Showing papers in "Circulation-cardiovascular Imaging in 2009"

Prediction of all-cause mortality from global longitudinal speckle strain: comparison with ejection fraction and wall motion scoring.

Abstract: Background— Although global left ventricular systolic function is an important determinant of mortality, standard measures such as ejection fraction (EF) and wall motion score index (WMSI) have important technical limitations. The aim of this study was to compare global longitudinal speckle strain (GLS), an automated technique for measurement of long-axis function, with EF and WMSI for the prediction of mortality. Methods and Results— Of 546 consecutive individuals undergoing echocardiography for assessment of resting left ventricular function, 91 died over a period of 5.2±1.5 years. In addition to Simpson biplane EF, WMSI was determined by 2 experienced readers and GLS was calculated from 3 standard apical views using 2D speckle tracking. The incremental value of EF, WMSI, and GLS to significant clinical variables was assessed in nested Cox models. Clinical factors associated with outcome (model χ2=20.2) were age (hazard ratio [HR], 1.46; P 35% and those with and without wall motion abnormalities. A GLS ≥−12% was found to be equivalent to an EF ≤35% for the prediction of prognosis. Intraobserver and interobserver variations for EF and GLS were similar. Conclusions— GLS is a superior predictor of outcome to either EF or WMSI and may become the optimal method for assessment of global left ventricular systolic function. Received March 9, 2009; accepted July 17, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Infarct tissue heterogeneity assessed with contrast-enhanced MRI predicts spontaneous ventricular arrhythmia in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillator.

Abstract: Background— The relation between infarct tissue heterogeneity on contrast-enhanced MRI and the occurrence of spontaneous ventricular arrhythmia (or sudden cardiac death) is unknown. Therefore, the study purpose was to evaluate the predictive value of infarct tissue heterogeneity assessed with contrast-enhanced MRI on the occurrence of spontaneous ventricular arrhythmia with subsequent implantable cardioverter-defibrillator (ICD) therapy (as surrogate of sudden cardiac death) in patients with previous myocardial infarction. Methods and Results— Ninety-one patients (age, 65±11 years) with previous myocardial infarction scheduled for ICD implantation underwent cine MRI to evaluate left ventricular function and volumes and contrast-enhanced MRI for characterization of scar tissue (infarct gray zone as measure of infarct tissue heterogeneity, infarct core, and total infarct size). Appropriate ICD therapy was documented in 18 patients (20%) during a median follow-up of 8.5 months (interquartile range, 2.1 to 20.3). Multivariable Cox proportional hazards analysis revealed that infarct gray zone was the strongest predictor of the occurrence of spontaneous ventricular arrhythmia with subsequent ICD therapy (hazard ratio, 1.49/10 g; CI, 1.01 to 2.20; χ2=4.0; P =0.04). Conclusions— Infarct tissue heterogeneity on contrast-enhanced MRI is the strongest predictor of spontaneous ventricular arrhythmia with subsequent ICD therapy (as surrogate of sudden cardiac death) among other clinical and MRI variables, that is, total infarct size and left ventricular function and volumes, in patients with previous myocardial infarction. Received October 8, 2008; accepted March 19, 2009.

Left atrial function in diastolic heart failure.

Abstract: Background— Abnormalities in left ventricular (LV) structure and function occur in patients with diastolic heart failure (DHF). The reasons for the transition from asymptomatic dysfunction to heart failure need better definition, including noninvasive measurements that can detect the transition. Methods and Results— In 64 patients undergoing right heart catheterization, simultaneous echocardiographic imaging was performed. As a control group, 27 healthy subjects were included. There were 25 with ejection factor (EF) <50%, 20 in DHF, and 19 with normal EF and LV hypertrophy but not in heart failure (diastolic dysfunction). LV volumes, mass, left atrial (LA) volumes and EF, annular atrial velocity (a′), and LA strain during systole (LAS), and atrial contraction (LAA) were measured. The ratio of wedge pressure to LAS strain was used as an index of LA stiffness, as was the ratio of E/e′ to LAS strain. All 3 patient groups had increased LA volumes and depressed LA EF, a′, and LAA strain, with no significant difference between patients with DHF and diastolic dysfunction in LA systolic function indices, LV mass, LA volumes, LV, and arterial elastance. LAS strain was lower in patients with DHF, and LA stiffness (invasive and noninvasive) was higher (both P <0.01), related well to pulmonary artery systolic pressure ( r =0.79, P <0.001), and was most accurate in identifying DHF patients from those with diastolic dysfunction (invasive area under the curve: 0.93, noninvasive: 0.85). Conclusions— Patients with DHF have increased LV mass and LA volume in comparison with normal controls, but not versus patients with LV hypertrophy who are not in heart failure. On the other hand, LAS strain is significantly reduced and LA stiffness is the most accurate index in identifying patients with DHF. Received August 5, 2008; accepted October 17, 2008. # CLINICAL PERSPECTIVE {#article-title-2}

Adenosine stress 64-and 256-row detector computed tomography angiography and perfusion imaging a pilot study evaluating the transmural extent of perfusion abnormalities to predict atherosclerosis causing myocardial ischemia

Abstract: Background— Multidetector computed tomography coronary angiography (CTA) is a robust method for the noninvasive diagnosis of coronary artery disease. However, in its current form, CTA is limited in its prediction of myocardial ischemia. The purpose of this study was to test whether adenosine stress computed tomography myocardial perfusion imaging (CTP), when added to CTA, can predict perfusion abnormalities caused by obstructive atherosclerosis. Methods and Results— Forty patients with a history of abnormal single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) underwent adenosine stress 64-row (n=24) or 256-row (n=16) detector CTP and CTA. A subset of 27 patients had invasive angiography available for quantitative coronary angiography. CTA and quantitative coronary angiography were evaluated for stenoses ≥50%, and SPECT-MPI was evaluated for fixed and reversible perfusion deficits using a 17-segment model. CTP images were analyzed for the transmural differences in perfusion using the transmural perfusion ratio (subendocardial attenuation density/subepicardial attenuation density). The sensitivity, specificity, positive predictive value, and negative predictive value for the combination of CTA and CTP to detect obstructive atherosclerosis causing perfusion abnormalities using the combination of quantitative coronary angiography and SPECT as the gold standard was 86%, 92%, 92%, and 85% in the per-patient analysis and 79%, 91%, 75%, and 92% in the per vessel/territory analysis, respectively. Conclusions— The combination of CTA and CTP can detect atherosclerosis causing perfusion abnormalities when compared with the combination of quantitative coronary angiography and SPECT. Received August 13, 2008; accepted March 17, 2009.

Age-related left ventricular remodeling and associated risk for cardiovascular outcomes: the Multi-Ethnic Study of Atherosclerosis.

Abstract: Background— Age-related alterations of left ventricular (LV) structure and function that may predispose to cardiovascular events are not well understood. Methods and Results— We used cardiac MRI to...

Relationships among regional arterial inflammation, calcification, risk factors, and biomarkers: a prospective fluorodeoxyglucose positron-emission tomography/computed tomography imaging study.

Abstract: Background— Fluorodeoxyglucose positron-emission tomography (FDG PET) imaging of atherosclerosis has been used to quantify plaque inflammation and to measure the effect of plaque-stabilizing drugs....

Noninvasive assessment of myocardial perfusion.

Abstract: Noninvasive assessment of myocardial perfusion is important in the diagnosis and risk stratification of patients with known or suspected coronary artery disease (CAD). Although single-photon emission computed tomography (SPECT) is most commonly used, multiple modalities including myocardial contrast echocardiography (MCE), positron emission tomography (PET), cardiac MRI (CMR), and cardiac computed tomography (CT) have emerged as promising techniques. This article will critically evaluate the strengths and weakness of these modalities for evaluating myocardial perfusion. Myocardial perfusion is a highly regulated process that includes epicardial vessels, resistance vessels, and the endothelium. Endothelial dysfunction is an early manifestation of vascular disease and plays a role in the development of CAD.1 In normal coronaries, sympathetic stimulation causes a flow-mediated endothelium-dependent release of nitric oxide resulting in epicardial and arteriolar vasodilation. With endothelial dysfunction, vasoconstriction from acetylcholine predominates, resulting an attenuation or absence of the normal flow-mediated vasodilation.2 When coronary arteries are narrowed by atherosclerotic disease, coronary autoregulation attempts to normalize myocardial blood flow by reducing the resistance of distal perfusion beds to preserve adequate myocardial oxygen supply.3 A stenosis must exceed 85% to 90% of luminal diameter before significant reductions in resting blood flow occur.4 However, under vasodilator stimulus, maximal coronary flow has been shown to decrease with stenosis of >45% (Figure 1).4 This has been demonstrated clinically using quantitative PET myocardial perfusion imaging (MPI).5,6 Because perfusion is an early change in the ischemic cascade,7 stress modalities that assess coronary perfusion reserve have a higher sensitivity in detecting flow-limiting stenoses than analysis of stress-induced wall motion abnormalities or ECG changes alone.8 Abnormal coronary flow reserve with vasodilator stress in the absence of a significant coronary stenosis occurs and has been attributed to microvascular and/or endothelial dysfunction.9 Figure 1. Relationship between percent diameter stenosis and …

Validation of 3-Dimensional Speckle Tracking Imaging to Quantify Regional Myocardial Deformation

Abstract: Background— Three-dimensional speckle tracking imaging (3D-STI) has been introduced to assess regional left ventricular (LV) myocardial function. This study was designed to validate LV strain measurements by 3D-STI against data obtained by sonomicrometry. Methods and Results— In each of 10 anesthetized sheep, sonomicrometry crystals were implanted on the endocardium and epicardium at the LV basal, mid, and apical anterior and lateral walls. LV 3D-STI data sets were obtained from the apical approach at a frame rate of approximately 30 frames/s. Segmental longitudinal (LS), radial (RS), and circumferential strain (CS) measurements by 3D-STI were compared with those by sonomicrometry at baseline and during pharmacological stress tests (dobutamine and propranolol infusion) and acute myocardial ischemia induced by coronary artery occlusion. Data were available from 136 LS, 108 CS, and 175 RS measurements. Good correlations were observed between strain measurements by 3D-STI and those by sonomicrometry (LS: r =0.89, P <0.001; RS: r =0.84, P <0.001; CS: r =0.90, P <0.001). In each segmental study, significant correlations of the 3 strain components were observed (LS: r =0.65 to 0.68, P <0.001; RS: r =0.59 to 0.70, P <0.001; CS: r =0.71 to 0.78, P <0.001). Conclusions— The newly developed 3D-STI technique can estimate LV regional circumferential, longitudinal, and radial strain components with reasonable correlation to sonomicrometry data. This methodology could be applied clinically to assess alteration of myocardial function by accurately measuring strain in basal, mid, and apical LV segments, even during pharmacological and ischemic interventions. Therefore, 3D-STI appears to be a reliable tool to assess LV regional wall function. Received February 18, 2009; accepted September 2, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Influence of myocardial fibrosis on left ventricular diastolic function: noninvasive assessment by cardiac magnetic resonance and echo.

Abstract: Background— Fibrosis is a common end point of many pathological processes affecting the myocardium and may alter myocardial relaxation properties. By measuring myocardial fibrosis with cardiac magnetic resonance and diastolic function with Doppler echocardiography, we sought to define the influence of fibrosis on left ventricular diastolic function. Methods and Results— Two hundred four eligible subjects from 252 consecutive subjects undergoing late postgadolinium myocardial enhancement (LGE) cardiac magnetic resonance and Doppler echocardiography were investigated. Subjects with normal diastolic function exhibited no or minimal fibrosis (median LGE score, 0; interquartile range, 0 to 0). In contrast, the majority of patients with cardiomyopathy (regardless of underlying cause) had abnormal diastolic function indices and substantial fibrosis (median LGE score, 3; interquartile range, 0 to 6.25). Prevalence of LGE positivity by diastolic filling pattern was 13% in normal, 48% in impaired relaxation, 78% in pseudonormal, and 87% in restrictive filling ( P <0.0001). Similarly, LGE score was significantly higher in patients with deceleration time <150 ms ( P <0.012), and it progressively increased with increasing left ventricular filling pressure estimated by tissue Doppler imaging–derived E/E′ ( P <0.0001). After multivariate analysis, LGE remained significantly correlated with degree of diastolic dysfunction ( P =0.0001). Conclusions— Severity of myocardial fibrosis by LGE significantly correlates with the degree of diastolic dysfunction in a broad range of cardiac conditions. Noninvasive assessment of myocardial fibrosis may provide valuable insights into the pathophysiology of left ventricular diastolic function and therapeutic response. Received November 25, 2008; accepted August 5, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Aortopulmonary collaterals after bidirectional cavopulmonary connection or Fontan completion: quantification with MRI.

Abstract: Background— Aortopulmonary collaterals (APCs) have been associated with increased morbidity after the Fontan operation. We aimed to quantify APC flow after bidirectional cavopulmonary connections and Fontan completions, using phase-contrast MRI, and to identify risk factors for the development of APCs. Methods and Results— APC blood flow was quantifiable in 24 of 36 retrospectively analyzed MRI studies. Sixteen studies were performed after the bidirectional cavopulmonary connections (group A) and 8 after the Fontan operation (group B). APC blood flow was calculated by subtracting the blood flow volume through the pulmonary arteries from that through the pulmonary veins. The ratio of pulmonary to systemic blood flow (Qp/Qs) was 0.93±0.26 in group A and 1.27±0.16 in group B. APC flow was 1.42 (0.58 to 3.83) L/min/m2 and 0.82 (0.50 to 1.81) L/min/m2 in groups A and B, respectively. The mean inaccuracies corresponded to 7.9±14.5% and 7.1±13.6% of ascending aortic flow in groups A and B, respectively. Qp/Qs was negatively correlated with a younger age at the time of the bidirectional cavopulmonary connections operation ( r =0.62, P =0.01) and positively correlated with the age at the time of the Fontan completion ( r =0.81, P =0.01). Patients with a previous right-sided modified Blalock-Taussig shunt had more collateral flow to the right lung than those without. Conclusions— APC blood flow can be noninvasively measured in bidirectional cavopulmonary connections and Fontan patients, using MRI in the majority of patients and results in a significant left-to-right shunt. Received November 8, 2008; accepted March 23, 2009.

Cardiac Mechanics in Mild Hypertensive Heart Disease: A Speckle - Strain Imaging Study

Abstract: Background— We hypothesized that abnormalities in regional systolic strain (e) might be present among hypertensive subjects with normal ejection fraction, and, if present, could be used to identify patients at high risk for heart failure. The aim of the current case-control study was to use speckle tracking imaging to identify subclinical global and regional systolic function abnormalities in hypertensive subjects with normal ejection fraction. Methods and Results— Standard 2D Doppler echocardiography, tissue Doppler imaging, and 2D speckle strain imaging were performed in 52 hypertensive subjects with normal ejection fraction and 52 control subjects of similar age. Peak systolic (S′), and diastolic (E′) annular velocities were obtained by tissue Doppler imaging, whereas longitudinal myocardial systolic velocity (V l ) and circumferential, longitudinal, and radial strains (e c , e l , e r ) were obtained by speckle tracking. Midwall shortening and peak basal longitudinal strain (e l ) were used as indices of regional function. Hypertensive subjects had lower velocities—tissue Doppler imaging E′ and S′, and V l —and evidence of reduced regional function. Surprisingly, however, global e values did not differentiate hypertensive subjects from control subjects. Among hypertensive patients, significant inverse associations were found between left ventricular mass and global longitudinal and circumferential e (both P Conclusions— Hypertensive heart disease with normal ejection fraction is associated with reduced myocardial velocities and reduced regional function but normal global e. Our data suggest that velocity abnormalities occur early in hypertension and may be an appropriate target for preventive strategies because they occur before abnormalities in global e.

Diagnostic accuracy and impact of computed tomographic coronary angiography on utilization of invasive coronary angiography.

Abstract: Background—Computed tomographic coronary angiography (CTA), given its high negative predictive value, is a potential gatekeeper for invasive coronary angiography (ICA). Before CTA can be further accepted into clinical practice, its impact on healthcare resources needs to be better understood. We sought to determine the clinical impact of CTA on ICA referrals, CTA accuracy, and normalcy rate. Methods and Results—To determine the impact of CTA, consecutive patients (n7017) undergoing ICA before and after implementing a dedicated cardiac CT program were reviewed and compared with 3 other centers (n11 508). To determine CTA accuracy, we evaluated consecutive CTA patients who underwent ICA. For normalcy rate, we identified patients with a low pretest probability for obstructive coronary artery disease. With the implementation of a cardiac CT program, the frequency of normal ICA decreased from 31.5% (1114 of 3538 patients) to 26.8% (932 of 3479 patients) (P0.001). These findings were significantly different (P0.003) from the 3 centers, in which normal ICAs were unchanged (30.0% [1870 of 6224 patients] to 31.0% [1642 of 5284 patients]). CTA had excellent per-patient sensitivity (99% [CI, 95% to 100%]), positive predictive value (92% [CI, 86% to 96%]) and negative predictive value (95% [CI, 72% to 100%]). Because of referral bias, specificity (64% [CI, 44% to 81%]) was low; however, the normalcy rate of CTA was 94% (CI, 90% to 97%). After adjusting for referral bias, the adjusted sensitivity was 90% (CI, 89% to 91%), and the adjusted specificity was 95% (CI, 94% to 96%), with positive and negative predictive values of 92% (CI, 91% to 93%) and 93% (CI, 92% to 94%), respectively. Conclusion—The clinical implementation of CTA appears to positively impact ICA by reducing the frequency of normal ICA. The operating characteristics of CTA support its potential role as a tool useful in ruling out obstructive coronary artery disease. (Circ Cardiovasc Imaging. 2009;2:16-23.)

Evaluation of alphavbeta3 integrin-targeted positron emission tomography tracer 18F-galacto-RGD for imaging of vascular inflammation in atherosclerotic mice.

Abstract: Background— 18F-Galacto-RGD is a positron emission tomography (PET) tracer binding to αvβ3 integrin that is expressed by macrophages and endothelial cells in atherosclerotic lesions. Therefore, we evaluated 18F-galacto-RGD for imaging vascular inflammation by studying its uptake into atherosclerotic lesions of hypercholesterolemic mice in comparison to deoxyglucose. Methods and results— Hypercholesterolemic LDLR−/−ApoB100/100 mice on a Western diet and normally fed adult C57BL/6 control mice were injected with 18F-galacto-RGD and 3H-deoxyglucose followed by imaging with a small animal PET/CT scanner. The aorta was dissected 2 hours after tracer injection for biodistribution studies, autoradiography, and histology. Biodistribution of 18F-galacto-RGD was higher in the atherosclerotic than in the normal aorta. Autoradiography demonstrated focal 18F-galacto-RGD uptake in the atherosclerotic plaques when compared with the adjacent normal vessel wall or adventitia. Plaque-to-normal vessel wall ratios were comparable to those of deoxyglucose. Although angiogenesis was not detected, 18F-galacto-RGD uptake was associated with macrophage density and deoxyglucose accumulation in the plaques. Binding to atherosclerotic lesions was efficiently blocked in competition experiments. In vivo imaging visualized 18F-galacto-RGD uptake colocalizing with calcified lesions of the aortic arch as seen in CT angiography. Conclusions— 18F-Galacto-RGD demonstrates specific uptake in atherosclerotic lesions of mouse aorta. In this model, its uptake was associated with macrophage density. 18F-Galacto-RGD is a potential tracer for noninvasive imaging of inflammation in atherosclerotic lesions. Received December 23, 2008; accepted May 11, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

A Study of Functional Anatomy of Aortic-Mitral Valve Coupling Using 3D Matrix Transesophageal Echocardiography

Abstract: Background— Mitral and aortic valves are known to be coupled via fibrous tissue connecting the two annuli. Previous studies evaluating this coupling have been limited to experimental animals using invasive techniques. The new matrix array transesophageal transducer provides high-resolution real-time 3D images of both valves simultaneously. We sought to develop and test a technique for quantitative assessment of mitral and aortic valve dynamics and coupling. Methods and Results— Matrix array transesophageal (Philips iE33) imaging was performed in 24 patients with normal valves who underwent clinically indicated transesophageal echocardiography. Custom software was used to detect and track the mitral and aortic annuli in 3D space throughout the cardiac cycle, allowing automated measurement of changes in mitral and aortic valve morphology. Mitral annulus surface area and aortic annulus projected area changed reciprocally over time. Mitral annulus surface area was 8.0±2.1 cm2 at end-diastole and decreased to 7.7±2.1 cm2 in systole, reaching its maximum (10.0±2.2 cm2) at mitral valve opening. Aortic annulus projected area was 4.1±1.2 cm2 at end-diastole, then increased during isovolumic contraction reaching its maximum (4.8±1.3 cm2) in the first third of systole and its minimum (3.6±1.0 cm2) during isovolumic relaxation. The angle between the mitral and aortic annuli was maximum (136±13°) at end-diastole and decreased to its minimum value (129±11°) during systole. Conclusions— This is the first study to report quantitative 3D assessment of the mitral and aortic valve dynamics from matrix array transesophageal images and describe the mitral-aortic coupling in a beating human heart. This ability may have impact on patient evaluation for valvular surgical interventions and prosthesis design. Received May 19, 2008; accepted November 6, 2008. # CLINICAL PERSPECTIVE {#article-title-2}

Age- and Gender-Specific Changes in the Left Ventricular Relaxation A Doppler Echocardiographic Study in Healthy Individuals

Abstract: Background—Although left ventricular diastolic function has been shown to deteriorate with advancing age, its gender-specific change is unknown. The aim of this study was to investigate age- and gender-specific changes in tissue Doppler–derived left ventricular diastolic index, E. Methods and Results—A total of 1333 healthy individual without known heart disease or hypertension (mean age, 55 years; range, 10 to 89) were enrolled and studied. Peak early mitral annular velocity (E) and peak late mitral annular velocity (A) were recorded and measured. As an index of the left ventricular relaxation, E was used. As an index of the left ventricular filling pressure, E/E was calculated. Although systolic indices poorly correlated with age, diastolic indices correlated well with age. Among those aged 30 to 39 and 40 to 49 years, E was significantly lower in males than in females. In subjects aged 50 to 59 and 60 to 69 years, E was similar in both genders. Among those aged 70 to 79 and 80 to 89 years, E was significantly lower in females than in males. Predictors of the lowest quartile of E among subjects aged 50 years were age (P0.0001; 2 66.11; odds ratio, 1.08; 95% CI, 1.058 to 1.097) and female gender (P0.002; 2 9.23; odds ratio, 1.68; 95% CI, 1.202 to 2.343). Conclusion—Age-related changes in diastolic indices were gender specific. In the elderly population, diastolic function deteriorated more significantly in the female gender than in the male gender. These results may explain the relatively higher incidence in elderly females among patients with diastolic heart failure and higher cardiovascular mortality in the female gender. (Circ Cardiovasc Imaging. 2009;2:41-46.)

Diffusion Spectrum MRI Tractography Reveals the Presence of a Complex Network of Residual Myofibers in Infarcted Myocardium

Abstract: Background— Changes in myocardial microstructure are important components of the tissue response to infarction but are difficult to resolve with current imaging techniques. A novel technique, diffu...

Rapid initial reduction of hyperenhanced myocardium after reperfused first myocardial infarction suggests recovery of the peri-infarction zone: one-year follow-up by MRI.

Abstract: Background— The time course and magnitude of infarct involution, functional recovery, and normalization of infarct-related electrocardiographic (ECG) changes after acute myocardial infarction (MI) are not completely known in humans. We sought to explore these processes early after MI and during infarct-healing using cardiac MRI. Methods and Results— Twenty-two patients with reperfused first-time MI were examined by MRI and ECG at 1, 7, 42, 182, and 365 days after infarction. Global left ventricular function and regional wall thickening were assessed by cine MRI, and injured myocardium was depicted by delayed contrast-enhanced MRI. Infarct size by ECG was estimated by QRS scoring. The reduction of hyperenhanced myocardium occurred predominantly during the first week after infarction (64% of the 1-year reduction). Furthermore, during the first week the amount of nonhyperenhanced myocardium increased significantly ( P <0.001), although the left ventricular mass remained unchanged. Left ventricular ejection fraction increased gradually, whereas the greater the regional transmural extent of hyperenhancement at day 1, the later the recovery of regional wall thickening. Regional wall thickening decreased progressively with increasing initial transmural extent of hyperenhancement ( P trend<0.0001). The time course and magnitude of decrease in QRS score corresponded with the reduction of hyperenhanced myocardium. Conclusions— The early reduction of hyperenhanced myocardium may reflect recovery of hyperenhanced, reversibly injured myocardium, which must be considered when predicting functional recovery from delayed contrast-enhanced MRI findings early after infarction. Also, the time course and magnitude for reduction of hyperenhanced myocardium were associated with normalization of infarct-related ECG changes. Received June 26, 2008; accepted November 19, 2008. # CLINICAL PERSPECTIVE {#article-title-2}

Sequential changes of myocardial microstructure in patients postmyocardial infarction by diffusion-tensor cardiac MR: correlation with left ventricular structure and function.

Abstract: Background— We used diffusion-tensor cardiac MR to investigate myocardial microstructure changes, including tissue integrity (mean diffusivity [MD], fractional anisotropy) and fiber architecture (h...

Molecular MRI of cardiomyocyte apoptosis with simultaneous delayed-enhancement MRI distinguishes apoptotic and necrotic myocytes in vivo: potential for midmyocardial salvage in acute ischemia.

Abstract: Background— A novel dual-contrast molecular MRI technique to image both cardiomyocyte apoptosis and necrosis in vivo within 4 to 6 hours of ischemia is presented. The technique uses the annexin-based nanoparticle AnxCLIO-Cy5.5 (apoptosis) and simultaneous delayed-enhancement imaging with a novel gadolinium chelate, Gd-DTPA-NBD (necrosis). Methods and Results— Mice with transient coronary ligation were injected intravenously at the onset of reperfusion with AnxCLIO-Cy5.5 (n=7) or the control probe Inact\_CLIO-Cy5.5 (n=6). T2*-weighted MR images (9.4 T) were acquired within 4 to 6 hours of reperfusion. The contrast-to-noise ratio between injured and uninjured myocardium was measured. The mice were then injected with Gd-DTPA-NBD, and delayed-enhancement imaging was performed within 10 to 30 minutes. Uptake of AnxCLIO-Cy5.5 was most prominent in the midmyocardium and was significantly greater than that of Inact\_CLIO-Cy5.5 (contrast-to-noise ratio, 8.82±1.5 versus 3.78±1.1; P <0.05). Only 21±3% of the myocardium with accumulation of AnxCLIO-Cy5.5 showed delayed-enhancement of Gd-DTPA-NBD. Wall thickening was significantly reduced in segments with delayed enhancement and/or transmural accumulation of AnxCLIO-Cy5.5 ( P <0.001). Fluorescence microscopy of AnxCLIO-Cy5.5 and immunohistochemistry of Gd-DTPA-NBD confirmed the presence of large numbers of apoptotic but potentially viable cardiomyocytes (AnxCLIO-Cy5.5 positive, Gd-DTPA-NBD negative) in the midmyocardium. Conclusions— A novel technique to image cardiomyocyte apoptosis and necrosis in vivo within 4 to 6 hours of injury is presented and reveals large areas of apoptotic but viable myocardium in the midmyocardium. Strategies to salvage the numerous apoptotic but potentially viable cardiomyocytes in the midmyocardium in acute ischemia should be investigated. Received February 19, 2009; accepted September 23, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Left Atrial Volume and Geometry in Healthy Aging The Cardiovascular Health Study

Abstract: Background— The left atrium is a validated marker of clinical and subclinical cardiovascular disease. Left atrial enlargement is often seen among older individuals; however, there are few population-based data regarding normal left atrial size among older persons, especially from those who are healthy, and from women. Furthermore, because the left atrium is a 3D structure, the commonly used parasternal long-axis diastolic diameter often underdiagnoses left atrial enlargement. Methods and Results— We evaluated left atrial size in 230 healthy participants (mean age, 76±5 years) free of prevalent cardiac disease, rhythm abnormality, hypertension, and diabetes selected from the Cardiovascular Health Study, a prospective community-based study of risk factors for cardiovascular disease in 5888 elderly participants. In addition to the standard long-axis measurement, we obtained left atrial superoinferior and lateral diameters and used these dimensions to estimate left atrial volume. These measurements were used to generate reference ranges for determining left atrial enlargement in older men and women, based on the 95% percentiles of the left atrial dimensions in healthy participants, both unadjusted, and after adjustment for age, height, and weight. In healthy elderly subjects, indices of left atrial size do not correlate with age or height but with weight and other measures of body build. Conclusions— These data provide normative reference values for left atrial size in healthy older women and men. The results should be useful for refining diagnostic criteria for left atrial dilation in the older population and may be relevant for cardiovascular risk stratification. Received October 7, 2008; accepted March 31, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Noninvasive quantification of systemic-to-pulmonary collateral flow: a major source of inefficiency in patients with superior cavopulmonary connections.

Abstract: Background— Systemic-to-pulmonary collateral flow (SPCF) is common in single-ventricle patients with superior cavopulmonary connections (SCPC). Because no validated method to quantify SPCF exists, neither its hemodynamic burden nor its clinical impact can be systematically evaluated. We hypothesize that (1) the difference in total ascending aortic (Ao) and caval flow (superior vena cava [SVC]+inferior vena cava [IVC]) and (2) the difference between pulmonary vein and pulmonary artery flow (PV−PA) provide 2 independent estimators of SPCF. Methods and Results— We measured Ao, SVC, IVC, right (RPA) and left (LPA) PA, and left (LPV) and right (RPV) PV flows in 17 patients with SCPC during routine cardiac MRI studies using through-plane phase-contrast velocity mapping. Two independent measures of SPCF were obtained: model 1, Ao−(SVC+IVC); and model 2, (LPV−LPA)+(RPV−RPA). Values were normalized to body surface area, Ao, and PV, and comparisons were made using linear regression and Bland-Altman analysis. SPCF ranged from 0.2 to 1.4 L/min for model 1 and 0.2 to 1.6 L/min for model 2, for an average indexed SPCF of 0.5 to 2.8 L/min/m2: 11% to 53% (mean, 37%) of Ao and 19% to 77% (mean, 54%) of PV. The mean difference between model 1 and model 2 was 0.01 L/min ( P =0.40; 2-SD range, −0.45 to 0.47 L/min). Conclusions— We present a noninvasive method for SPCF quantification in patients with SCPC. It should provide an important clinical tool in treating these patients. Furthermore, we show that SPCF is a significant hemodynamic burden in many patients with bidirectional Glenn shunt physiology. Future investigations will allow objective study of the impact of collateral flow on outcome. Received November 10, 2008; accepted July 7, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Alteration in left ventricular strains and torsional mechanics after ultralong duration exercise in athletes.

Abstract: Background— Numerous studies have reported evidence of cardiac injury associated with transient left ventricular (LV) systolic and diastolic dysfunction after prolonged and strenuous exercise. We used 2D ultrasound speckle tracking imaging to evaluate the effect of an ultralong-duration exercise on LV regional strains and torsion. We speculated that systolic dysfunction after exercise is associated with depressed LV strains and torsion, and diastolic dysfunction results from decreased and delayed untwisting, a key factor of LV suction and early filling. Methods and Results— Twenty-three triathletes underwent conventional and speckle tracking imaging echocardiography at rest before and immediately after an ultralong distance triathlon. Measurements included LV longitudinal, circumferential and radial strains, LV rotations, and LV torsion. After the race, LV systolic dysfunction was characterized by a decrease in LV longitudinal, radial, and circumferential strains, especially for apical radial strains (44.6±15.1% versus 31.1±13.8%, P <0.001). Peak torsion was slightly decreased (8.3±5.1° versus 6.4±3.9°, respectively, P =0.09) and significantly delayed (91±18% versus 128±31% of systolic duration, P <0.001) beside end-ejection. Peak untwisting was also depressed and delayed beside isovolumic relaxation. Conclusions— This study documented major alterations in cardiac strains and torsion after an ultralong distance triathlon. LV systolic strains were depressed but not delayed, whereas twisting was decreased and delayed. This altered pattern hampered the rapid untwisting during isovolumic relaxation phase, reducing LV diastolic suction and early filling. Received July 30, 2008; accepted May 18, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Impact of mild hypertension on left atrial size and function

Abstract: Background— Left atrial (LA) enlargement has been documented to occur in moderate and severe hypertension. Methods and Results— One hundred twelve mild hypertension patients were prospectively recruited and compared with 198 healthy volunteers. All recruits had a transthoracic echocardiogram. Maximum LA biplane volume, minimum LA biplane volume, and pre ‘p’-LA biplane volume were measured, and left atrial passive, active emptying, and conduit volumes were calculated at baseline and in a subgroup of patients after 12 months. After adjusting for age, gender, and body mass index, maximum LA biplane volume, pre ‘p’-LA biplane volume, and their indexed volumes were increased in the hypertension group. Active emptying volume and fraction were significantly increased in the hypertension group, with no change in conduit and passive volumes. Subgroup analysis comparing hypertensives with normal/mildly increased left ventricular mass (group 1) with those with moderate/severely increased left ventricular mass (group 2) at baseline demonstrated that maximum LA biplane volume (62.8±17.9 mL versus 45.4±13.7 mL; P <0.001) was significantly increased in group 2. Active emptying volume was also increased. Conclusion— Even mild hypertension seems to be associated with a reduction in early diastolic filling. This results in augmented late left ventricular diastolic filling due to active atrial contraction and may be the mechanism for the increase in left atrial size. Received May 21, 2008; accepted January 2, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

In vivo quantification of carotid artery wall dimensions: 3.0-Tesla MRI versus B-mode ultrasound imaging.

Abstract: Background— Our aim was to compare common carotid mean wall thickness (MWT) measurements by 3.0-T MRI with B-mode ultrasound common carotid intima-media thickness (CCIMT) measurements, a validated surrogate marker for cardiovascular disease. Methods and Results— B-mode ultrasound and 3.0-T MRI scans of the left and right common carotid arteries were repeated 3 times in 15 healthy younger volunteers (age, 26±2.6 years), 15 healthy older volunteers (age, 57±3.2 years), and 15 subjects with cardiovascular disease and carotid atherosclerosis (age, 63±9.8 years). MWT was 0.711 (SD, 0.229) mm and mean CCIMT was 0.800 (SD, 0.206) mm. MWT and CCIMT were highly correlated ( r =0.89, P <0.001). The intraclass correlation coefficients for interscan and interobserver and intraobserver agreements of MRI MWT measurements were larger than 0.95 with small confidence intervals, indicating excellent reproducibility. Power calculations indicate that 89 subjects are required to detect a 4% difference in MRI MWT compared with 469 subjects to detect similar differences with ultrasound IMT in follow-up studies. Conclusions— The study data for carotid MRI and ultrasound IMT showed strong agreement, indicating that both modalities measure the thickness of the intima and media. The advantage of MRI over ultrasound is that the measurement variability is smaller, enabling smaller sample sizes and potentially shorter study duration in cardiovascular prevention trials. Received April 28, 2008; accepted January 26, 2009.

Automated segmentation of routine clinical cardiac magnetic resonance imaging for assessment of left: Ventricular diastolic dysfunction

Abstract: Background— Cardiac magnetic resonance (CMR) is established for assessment of left ventricular (LV) systolic function but has not been widely used to assess diastolic function. This study tested performance of a novel CMR segmentation algorithm (LV-METRIC) for automated assessment of diastolic function. Methods and Results— A total of 101 patients with normal LV systolic function underwent CMR and echocardiography (echo) within 7 days. LV-METRIC generated LV filling profiles via automated segmentation of contiguous short-axis images (204±39 images, 2:04±0:53 minutes). Diastolic function by CMR was assessed via early:atrial filling ratios, peak diastolic filling rate, time to peak filling rate, and a novel index—diastolic volume recovery (DVR), calculated as percent diastole required for recovery of 80% stroke volume. Using an echo standard, patients with versus without diastolic dysfunction had lower early:atrial filling ratios, longer time to peak filling rate, lower stroke volume–adjusted peak diastolic filling rate, and greater DVR (all P <0.05). Prevalence of abnormal CMR filling indices increased in relation to clinical symptoms classified by New York Heart Association functional class ( P =0.04) or dyspnea ( P =0.006). Among all parameters tested, DVR yielded optimal performance versus echo (area under the curve: 0.87±0.04, P <0.001). Using a 90% specificity cutoff, DVR yielded 74% sensitivity for diastolic dysfunction. In multivariate analysis, DVR (odds ratio, 1.82; 95% CI, 1.13 to 2.57; P =0.02) was independently associated with echo-evidenced diastolic dysfunction after controlling for age, hypertension, and LV mass (χ2=73.4, P <0.001). Conclusions— Automated CMR segmentation can provide LV filling profiles that may offer insight into diastolic dysfunction. Patients with diastolic dysfunction have prolonged diastolic filling intervals, which are associated with echo-evidenced diastolic dysfunction independent of clinical and imaging variables. Received May 11, 2009; accepted September 16, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Mechanism of Decrease in Mitral Regurgitation After Cardiac Resynchronization Therapy: Optimization of the Force–Balance Relationship

Abstract: Background— Cardiac resynchronization therapy (CRT) has been shown to reduce functional mitral regurgitation (MR). It has been proposed that the mechanism of MR reduction relates to geometric change or, alternatively, changes in left ventricular (LV) contractile function. Normal mitral valve (MV) function relies on a balance between tethering and closing forces on the MV leaflets. Functional MR results from a derangement of this force–balance relationship, and CRT may be an important modulator of MV function by its ability to enhance the force–balance relationship on the MV. We hypothesized that CRT improves the comprehensive force balance acting on the valve, including favorable changes in both geometry and LV contractile function. Methods and Results— We examined the effect of CRT on 34 patients with functional MR before and after CRT (209±81 days). MR regurgitant volume, closing forces on MV (derived from Doppler transmitral pressure gradients), including dP/dt and a factor (closing pressure ratio) expressing how long the peak closing gradient is maintained over systole (closing pressure ratio=velocity time integral/MR peak velocity×mitral regurgitation time), and dyssynchrony by tissue Doppler were measured. End-diastolic volume, end-systolic volume, mitral valve annular area (MAA) and contraction (percent change in MAA from end-diastole to midsystole), leaflet closing area (leaflet area during valve closure), and tenting volume (volume under leaflets to annular plane) were measured by 3D echocardiography. After CRT, end-diastolic volume (253±111 versus 221±110 mL, P <0.001) and end-systolic volume (206±97 versus 167±91 mL, P <0.001) decreased and ejection fraction (19±6 versus 27±9%, P <0.001) increased. MR regurgitant volume decreased from 35±17 to 23±14 mL ( P <0.001), MAA from 11.6±3.5 to 10.5±3.1 cm2 ( P <0.001), leaflet closing area from 15.4±5 to 13.7±3.8 cm2 ( P <0.001), and tenting volume from 5.7±2.6 to 4.6±2.2 mL ( P <0.001). Peak velocity (and therefore transmitral closing pressure) was more sustained throughout systole, as reflected by the increase in the closing pressure ratio (0.77±0.1 versus 0.84±0.1 before CRT versus after CRT, P =0.01); dP/dt also improved after CRT. There was no change in dyssynchrony or MAA contraction. Conclusions— Reduction in MR after CRT is associated with favorable changes in MV geometry and closing forces on the MV. It does so by favorably affecting the force balance acting on the MV in 2 ways: reducing tethering through reversal of LV remodeling and increasing the systolic duration of peak transmitral closing pressures. Received October 9, 2008; accepted September 5, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Apical rotation assessed by speckle-tracking echocardiography as an index of global left ventricular contractility.

Abstract: Background— Left ventricular (LV) apical rotation and twist can be estimated noninvasively by speckle-tracking echocardiography (STE). In this study, we tested whether apical rotation is an accurate index of LV contractility. Methods and Results— We measured LV basal and apical rotation by STE in 11 open-chest anesthetized mongrel dogs under 8 different inotropic stages before and after ligation of either left anterior descending (n=6) or circumflex coronary artery (n=5). We measured LV pressure simultaneously with a high-fidelity pressure catheter and calculated LV ejection fraction (EF) with the biplane Simpson method and 2D echocardiography. Maximal positive dP/dt (dP/dtmax) was used as the gold standard measurement of LV contractility. We compared LV twist and apical rotation and EF against dP/dtmax by linear mixed model. LV apical rotation and twist showed dose-dependent increases and decreases after dobutamine and esmolol infusion, respectively. However, basal rotation did not change significantly during different inotropic conditions. There was a stronger association between dP/dtmax and LV twist ( R 2=0.747, P <0.001) and apical rotation ( R 2=0.726, P <0.001) than between dP/dtmax and EF ( R 2=0.408, P <0.001), and this trend was more apparent with coronary ligation irrespective of the ligation site. There was also a high association between dP/dtmax and apical rotation alone, both with ( R 2=0.805, P <0.001) and without ( R 2=0.748, P <0.001) coronary ligation. Apical rotation alone showed comparable accuracy to LV twist. Apical rotational velocity also showed a high association with dP/dtmax ( R 2=0.669, P <0.001) and LV twist ( R 2=0.892, P <0.001). Conclusions— Apical rotation assessed by STE is an effective noninvasive index of global LV contractility and is more closely related to dP/dtmax than LV EF. Received May 27, 2008; accepted November 30, 2008. # CLINICAL PERSPECTIVE {#article-title-2}

Prevalence of coronary artery disease assessed by multislice computed tomography coronary angiography in patients with paroxysmal or persistent atrial fibrillation

Abstract: Background— Although atrial fibrillation (AF) has been linked to underlying coronary artery disease (CAD), data supporting this association have been based on ECG and clinical history for the definition of CAD rather than direct visualization of atherosclerosis. Methods and Results— The prevalence of CAD among patients with paroxysmal or persistent AF and without history of CAD was evaluated using multislice computed tomography. Multislice computed tomography was performed in 150 patients with AF (61±11 years, 67% males, 58% asymptomatic) with predominantly low (59%) or intermediate (25%) pretest likelihood of CAD. CAD was classified as obstructive (≥50% luminal narrowing) or not. A population of 148 patients without history of AF, similar to the AF group as to age, gender, symptomatic status, and pretest likelihood, served as a control group. Logistic regression analysis was applied to evaluate the relationship between demographic and clinical data and the presence of obstructive CAD. On the basis of multislice computed tomography, 18% of patients with AF were classified as having no CAD, whereas 41% showed nonobstructive CAD and the remaining 41% had obstructive CAD. Among patients without AF, 32% were classified as having no CAD, whereas 41% showed nonobstructive CAD and 27% had obstructive CAD ( P =0.010 compared with patients with AF). At logistic regression analysis, age, male gender, and the presence of AF were significantly related to obstructive CAD. Conclusion— A higher prevalence of obstructive CAD was observed among patients with AF, confirming the hypothesis that AF could be a marker of advanced coronary atherosclerosis. Received June 26, 2008; accepted January 2, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Multislice Computed Tomography in the Exclusion of Coronary Artery Disease in Patients With Presurgical Valve Disease

Abstract: Background— Multislice computed tomography (MSCT) has shown high negative predictive value in ruling out obstructive coronary artery disease. Preliminary studies in patients with valvular heart disease (VHD) have demonstrated the potential of MSCT angiography (CTA) in such patients, precluding need for invasive angiography (XA). However, larger prospectively designed studies, including patients with atrial fibrillation and incorporating dose reduction algorithms, are needed. Methods and Results— To evaluate the clinical utility of 64-slice CT in the preoperative assessment in patients with VHD, we prospectively studied 452 consecutive patients undergoing routine cardiac catheterization for eligibility. Two hundred thirty-seven patients underwent both MSCT and XA. Segment-based, vessel-based, and patient-based agreement between CTA and XA was estimated assuming that “nonevaluable” segments were positive for significant coronary stenosis. In a patient-based analysis, sensitivity, specificity, positive predictive value, and negative predictive values of CTA were 95%, 89%, 66%, and 99%, respectively; in vessel-based analysis, 90%, 92%, 48%, and 99%, respectively; and in segment-based analysis, 89%, 97%, 38%, and 100%, respectively. No significant differences were found between patients with or without atrial fibrillation. A CAC value of 390 was the best cutoff for the identification of patients with positive or inconclusive CTA (which would not be exempted from XA in the clinical setting). Conclusions— In the preoperative assessment of patients with predominant VHD, the diagnostic accuracy of 64-slice CTA for ruling out the presence of significant coronary artery disease is very good even when including patients with irregular heart rhythm. Using this approach, CAC quantification before CTA can be successfully used to identify patients who should be referred directly to XA, sparing unnecessary exposure to radiation. Received October 16, 2008; accepted March 30, 2009. # CLINICAL PERSPECTIVE {#article-title-2}

Correlates of carotid plaque presence and composition as measured by MRI: the Atherosclerosis Risk in Communities Study.

Abstract: Background— The composition of atherosclerotic plaque affects the likelihood of an atherothrombotic event, but prospective studies relating risk factors to carotid wall and plaque characteristics m...