Deformation Dynamics and Mechanical Properties of the Aortic Annulus by 4-Dimensional Computed Tomography Insights into the Functional Anatomy of the Aortic Valve Complex and Implications for Transcatheter Aortic Valve Therapy

OBJECTIVES: The purpose of this study was to assess deformation dynamics and in vivo mechanical properties of the aortic annulus throughout the cardiac cycle. Understanding dynamic aspects of functional aortic valve anatomy is important for beating-heart transcatheter aortic valve implantation.

METHODS: Thirty-five patients with aortic stenosis and 11 normal subjects underwent 256-slice computed tomography. The aortic annulus plane was reconstructed in 10% increments over the cardiac cycle. For each phase, minimum diameter, ellipticity index, cross-sectional area (CSA), and perimeter (Perim) were measured. In a subset of 10 patients, Young’s elastic module was calculated from the stress-strain relationship of the annulus.

RESULTS: In both subjects with normal and with calcified aortic valves, minimum diameter increased in systole (12.3 ± 7.3% and 9.8 ± 3.4%, respectively; p < 0.001), and ellipticity index decreased (12.7 ± 8.8% and 10.3 ± 2.7%, respectively; p < 0.001). The CSA increased by 11.2 ± 5.4% and 6.2 ± 4.8%, respectively (p < 0.001). Perim increase was negligible in patients with calcified valves (0.56 ± 0.85%; p < 0.001) and small even in normal subjects (2.2 ± 2.2%; p = 0.01). Accordingly, relative percentage differences between maximum and minimum values were significantly smallest for Perim compared with all other parameters. Young’s modulus was calculated as 22.6 ± 9.2 MPa in patients and 13.8 ± 6.4 MPa in normal subjects.

CONCLUSIONS: The aortic annulus, generally elliptic, assumes a more round shape in systole, thus increasing CSA without substantial change in perimeter. Perimeter changes are negligible in patients with calcified valves, because tissue properties allow very little expansion. Aortic annulus perimeter appears therefore ideally suited for accurate sizing in transcatheter aortic valve implantation.

PMID: 22222074

Prognostic Value of Routine Cardiac Magnetic Resonance Assessment of Left Ventricular Ejection Fraction and Myocardial Damage: An International, Multicenter Study

OBJECTIVES: Cardiac magnetic resonance (CMR) is considered the reference standard for assessment of left ventricular ejection fraction (LVEF) and myocardial damage.  However, few studies have evaluated the relationship between CMR findings and patient outcome, and of these, most are small and none multicenter.  We performed an international, multicenter study to assess the prognostic importance of routine CMR in patients with known or suspected heart disease.

METHODS: From 10 centers in 6 countries, consecutive patients undergoing routine CMR assessment of LVEF and myocardial damage by cine and delayed-enhancement imaging (DE-CMR), respectively, were screened for enrollment.  Clinical data, CMR protocol information, and findings were collected at all sites and submitted to the data coordinating center for verification of completeness and analysis.  The primary end point was all-cause mortality.

RESULTS: A total of 1560 patients (age, 59±14 years; 70% men) were enrolled.  Mean LVEF was 45±18%, and 1049 (67%) patients had hyperenhanced tissue (HE) on DE-CMR indicative of damage.  During a median follow-up time of 2.4 years (interquartile range, 1.2, 2.9 years), 176 (11.3%) patients died.  Patients who died were more likely to be older (P<0.0001), have coronary disease (P=0.004), have lower LVEF (P<0.0001), and have more segments with HE (P<0.0001).  In multivariable analysis, age, LVEF, and number of segments with HE were independent predictors of mortality.  Among patients with near-normal LVEF (≥50%), those with above-median HE (>4 segments) had reduced survival compared to patients with below- or at-median HE (P=0.02).

CONCLUSIONS: Both LVEF and amount of myocardial damage as assessed by routine CMR are independent predictors of all-cause mortality.  Even in patients with near-normal LVEF, significant damage identifies a cohort with a high risk for early mortality.

PMID: 21911738

Comparison of Severity of Aortic Regurgitation by Cardiovascular Magnetic Resonance Versus Transthoracic Echocardiography

OBJECTIVES: Transthoracic echocardiography is the current standard for assessing aortic regurgitation (AR).  AR severity can also be evaluated by flow measurement in the ascending aorta using cardiac magnetic resonance (CMR); however, the optimal site for flow measurement and the regurgitant fraction (RF) severity grading criteria that best compares with the transthoracic echocardiographic assessment of AR are not clear.  The present study aimed to determine the optimal site and RF grading criteria for AR severity using phase-contrast flow measurements and CMR.

METHODS: A prospective observational study was performed of 107 consecutive patients who were undergoing CMR of the thoracic aorta.  Using CMR, the AR severity and aortic dimensions were measured at 3 levels in the aorta (the sinotubular junction, mid-ascending aorta, and distal ascending aorta).

RESULTS: The results were compared to the transthoracic echocardiographic grade of AR severity using multiple qualitative and quantitative criteria (grade 0, none; I+, mild; II+, mild to moderate; III+, moderate to severe; and IV+, severe).  The mean RF values were significantly greater at the sinotubular junction than at the distal ascending aorta (13 ± 13.3% vs 9.4 ± 12.6%, respectively; p <0.001).  The RF values that best defined AR severity using phase-contrast CMR were as follows: grade 0 to I+, <8%; grade II+, 8% to 19%; grade III+, 20 to 29%; and grade IV+, 30%) at the sinotubular or mid-ascending aorta.

CONCLUSIONS: In conclusion, the quantitative RF values of AR severity using phase-contrast flow are best assessed in the proximal ascending aorta and differ from recognized quantitative echocardiographic criteria.

PMID: 21784393

Left Ventricular Structural Remodeling in Health and Disease: With Special Emphasis on Volume, Mass, and Geometry

The changes in left ventricular (LV) structure and geometry that evolve after myocardial injury or overload usually involve chamber dilation and/or hypertrophy. Such architectural remodeling can be classified as eccentric or concentric. Consideration of LV volume, mass, and relative wall thickness (or mass/volume) allows classification of LV remodeling that includes virtually all LV remodeling changes that are seen in health and disease. These various architectural changes generally include the development of LV hypertrophy in a pattern that is closely related to the type of injury or overload, and they are accompanied by differences in cardiac function and hemodynamics. Some patterns of remodeling are associated with adverse outcomes whereas others appear to be adaptive and physiologic without adverse consequences. Considering all patients with LV hypertrophy as a homogenous group is inconsistent with our understanding of the various remodeling patterns that are discussed in this review.

PMID: 21996383

Serial Doppler Echocardiography and Tissue Doppler Imaging in the Detection of Elevated Directly Measured Left Atrial Pressure in Ambulant Subjects With Chronic Heart Failure

OBJECTIVES:  Echocardiographic indexes including the ratio of transmitral to annular early diastolic velocities (E/e’) may identify raised invasively measured left ventricular filling pressures when tested in cross-sectional studies in some populations. The accuracy of these indexes when measured sequentially remains untested. We determined the accuracy of Doppler echocardiography and tissue Doppler imaging (TDI) measurements in detecting elevated directly measured left atrial pressure (LAP) in ambulant subjects with stable chronic heart failure.This study sought to determine the accuracy of Doppler echocardiography and TDI measurements in detecting elevated LAP in ambulant subjects with chronic heart failure using directly measured LAP as the reference.

METHODS:  Fifteen patients with New York Heart Association functional class II to III heart failure and a permanently implanted direct LAP monitoring device underwent serial echocardiography. Simultaneous resting mean LAP, Doppler mitral inflow, mitral annular TDI, and pulmonary venous inflow velocities were obtained on each occasion. Receiver-operator characteristic curve analysis was used to compare the accuracy of the Doppler variables to detect an elevated device LAP≥15 and ≥20 mm Hg.

RESULTS: The patients (13 men, mean age: 71 years, mean left ventricular ejection fraction: 32 ± 12%) underwent 60 simultaneous echocardiographic studies and LAP measurements with a median of 4 (1 to 7) studies per patient. Mean LAP was 16.9 (range 5 to 39 mm Hg) at
echocardiography (n = 60). E/e’ had the greatest accuracy for detection of LAP≥15 mm Hg with an area beneath the receiver-operator characteristic curve >0.9. In comparison, area under the curve for mitral E velocity and mitral E/A were 0.77 and 0.76, respectively (p<0.008 vs. E/e’ medial and average).

CONCLUSIONS:  Single and serial measurements of mitral inflow and mitral annular TDI velocities (E/e’) can reliably detect raised directly measured LAP in ambulant subjects with compensated chronic heart failure.

PMID: 21920328

Apical Hypertrophic Cardiomyopathy: Prevalence and Correlates of Apical Outpouching

OBJECITVES: Apical outpouching, including wall motion abnormalities and aneurysms, has been described in apical hypertrophic cardiomyopathy (ApHCM).

METHODS: Between 1976 and 2006, 193 patients with ApHCM (120 men; overall mean age, 61 ± 17 years) were evaluated.

RESULTS: Apical outpouching was found in 29 patients (15%) and in 22 of the 78 patients (28%) imaged with contrast echocardiography. Six patients had apical aneurysms, and 23 patients had hypokinesis with apical dilatation but no wall thinning. Apical outpouching was more common in patients with diastolic gradients out of the apex (P < .001), corrected QT interval prolongation (P < .001), increased apical wall thickness (P = .01), and family histories of sudden cardiac death (P = .03). Sudden cardiac death, resuscitated cardiac arrest, or discharge of an automated internal cardiac defibrillator, or a combination, was observed in 11 patients (6%) during follow-up. Atrial fibrillation (28%), ventricular tachycardia (20%), and stroke (11%) were also relatively common in this study. No difference was observed in overall mortality rate comparing patients with ApHCM with and without apical outpouching. Similarly, no differences were found in the rates of sudden cardiac death, resuscitated cardiac arrest, and discharge of an automated internal cardiac defibrillator. The impact of true aneurysms was not assessed in this study.

CONCLUSIONS: Cardiac complications appear commonly in patients with ApHCM, but they did not seem to be related to apical outpouching in the present analysis.

PMID: 21511435

Mitral and Tricuspid Annular Velocities in Constrictive Pericarditis and Restrictive Cardiomyopathy: Correlation With Pericardial Thickness on Computed Tomography

OBJECTIVES: The aims of this study were to: 1) compare early diastolic mitral annular velocity (E’) of septal annulus (SE’) with E’ of lateral mitral annulus (LE’) and right lateral tricuspid annulus (RE’) in patients with constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM); and 2) assess the relationship between pericardial thickness measured by computed tomography and lateral E’ velocity.The SE’ velocity has been shown to be able to distinguish CP from RCM. However, tissue Doppler parameters of LE’ and RE’ velocities in patients with CP have not been comprehensively analyzed in comparison with SE’. Moreover, the impact of pericardial thickness on the lateral annulus velocity has not been assessed.

METHODS: Thirty-seven patients with CP, 35 patients with RCM, and 70 normal controls were evaluated with echocardiography including SE’, LE’, and RE’. In CP, the maximal pericardial thicknesses on both left and right ventricle were measured by computed tomography.

RESULTS: Mean LE’/SE’ (ratio between mitral LE’ and SE’) was 0.94 ± 0.17 and RE’/SE’ (ratio between tricuspid RE’ and mitral SE’) was 0.81 ± 0.26 in patients with CP, which were lower than those in normal controls (LE’/SE’ 1.36 ± 0.24; RE’/SE’ 1.30 ± 0.32; both p < 0.001) and patients with RCM (LE’/SE’ 1.35 ± 0.31; RE’/SE’ 1.96 ± 0.71; both p < 0.001). There was a significant inverse correlation between right pericardial thickness and RE’ (ρ = -0.489; p = 0.002) and similar trend between left pericardial thickness and LE’ (ρ = -0.284; p = 0.089).

CONCLUSIONS: The ratio between lateral and septal E’ was significantly reduced in patients with CP compared with that in normal control patients and patients with RCM so that the reduced ratios of LE’/SE’ and RE’/SE’ appear to be a useful diagnostic parameter for CP. Moreover, reduced lateral E’ was correlated with the pericardial thickness on their respective sides.

PMID: 21679889

Association Between High-Sensitivity C-Reactive Protein and Coronary Plaque Subtypes Assessed by 64-Slice Coronary Computed Tomography Angiography in an Asymptomatic Population

PMID: 21422167

Troponin T Levels and Infarct Size by SPECT Myocardial Perfusion Imaging

OBJECTIVES: To evaluate the relationship between serial cardiac troponin T (cTnT) levels with infarct size and left ventricular ejection fraction by gated single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in patients with acute myocardial infarction (AMI). Current guidelines recommend the use of cTnT as the biomarker of choice for the diagnosis of AMI. Data relating cTnT to SPECT-MPI in patients with AMI are limited.

METHODS: A subset of patients with their first AMI participating in a community-based cohort of AMI in Olmsted County, Minnesota, were prospectively studied. Serial cTnT levels were evaluated at presentation, <12 h and 1, 2, and 3 days after onset of pain. Peak cTnT was defined as the maximum cTnT value.

RESULTS: A total of 121 patients (age, 61 ± 13 years; 31% women) with AMI underwent gated SPECT-MPI at a median (25th percentile, 75th percentile) of 10 (5, 15) days post-AMI. The type of infarct was non-ST-segment elevation myocardial infarction in 61%, and 13% were anterior in location. The median infarct size was 1% (0%, 11%) and the median gated left ventricular ejection fraction was 54% (47%, 60%). Fifty-nine patients (49% of the population) had no measurable infarction by SPECT-MPI. Independent predictors of measurable SPECT-MPI infarct size included cTnT at days 1, 2, and 3 and peak cTnT, but not at presentation or <12 h. In receiver-operator characteristic analysis, the area under the curve was highest at day 3. Receiver-operator characteristic analysis demonstrated a cutoff of 1.5 ng/ml for peak cTnT for the detection of measurable infarct size.

CONCLUSIONS: In a community-based cohort of patients with their first AMI, independent predictors of measurable SPECT-MPI infarct size included cTnT at days 1, 2, and 3 and peak cTnT. In contrast, cTnT level at presentation and <12 h was not an independent predictor of myocardial infarction size as assessed by SPECT-MPI. Receiver-operator characteristic analysis demonstrated a cutoff value peak cTnT of 1.5 ng/ml for the detection of measurable infarct.

PMID: 21565741

Diastolic Relaxation and Compliance Reserve During Dynamic Exercise in Heart Failure With Preserved Ejection Fraction

OBJECTIVES: Recent studies have examined haemodynamic changes with stressors such as isometric handgrip and rapid atrial pacing in heart failure with preserved ejection fraction (HFpEF), but little is known regarding left ventricular (LV) pressure-volume responses during dynamic exercise.  The objective is to assess LV haemodynamic responses to dynamic exercise in patients with HFpEF.

METHODS:  Twenty subjects with normal ejection fraction (EF) and exertional dyspnoea underwent invasive haemodynamic assessment during dynamic exercise to evaluate suspected HFpEF.

RESULTS:  LV end-diastolic pressure was elevated at rest (>15&emsp14; mmHg, n=18) and with exercise (≥20&emsp14;mmHg, n=20) in all subjects, consistent with HFpEF. Heart rate (HR), blood pressure, arterial elastance and cardiac output increased with exercise (all p<0.001).  Minimal and mean LV diastolic pressures increased by 43-56% with exercise (both p<0.0001), despite a trend towards a reduction in LV end-diastolic volume (p=0.08).  Diastolic filling time was abbreviated with increases in HR and the proportion of diastole that elapsed prior to estimated complete relaxation increased (p<0.0001), suggesting inadequate relaxation reserve relative to the shortening of diastole.  LV diastolic chamber elastance acutely increased 50% during exercise (p=0.0003).  Exercise increases in LV filling pressures correlated with changes in diastolic relaxation rates, chamber stiffness and arterial afterload but were not related to alterations in preload volume, HR or cardiac output.

CONCLUSIONS:  In patients with newly diagnosed HFpEF, LV filling pressures increase during dynamic exercise in association with inadequate enhancement of relaxation and acute increases in LV chamber stiffness.  Therapies that enhance diastolic reserve function may improve symptoms of exertional intolerance in patients with hypertensive heart disease and early HFpEF.

PMID: 21586744

Atherosclerosis in Ancient Egyptian Mummies the Horus Study

OBJECTIVES: The purpose of this study was to determine whether ancient Egyptians had atherosclerosis. The worldwide burden of atherosclerotic disease continues to rise and parallels the spread of diet, lifestyles, and environmental risk factors associated with the developed world. It is tempting to conclude that atherosclerotic cardiovascular disease is exclusively a disease of modern society and did not affect our ancient ancestors.

METHODS: We performed whole body, multislice computed tomography scanning on 52 ancient Egyptian mummies from the Middle Kingdom to the Greco-Roman period to identify cardiovascular structures and arterial calcifications. We interpreted images by consensus reading of 7 imaging physicians, and collected demographic data from historical and museum records. We estimated age at the time of death from the computed tomography skeletal evaluation.

RESULTS: Forty-four of 52 mummies had identifiable cardiovascular (CV) structures, and 20 of these had either definite atherosclerosis (defined as calcification within the wall of an identifiable artery, n = 12) or probable atherosclerosis (defined as calcifications along the expected course of an artery, n = 8). Calcifications were found in the aorta as well as the coronary, carotid, iliac, femoral, and peripheral leg arteries. The 20 mummies with definite or probable atherosclerosis were older at time of death (mean age 45.1 ± 9.2 years) than the mummies with CV tissue but no atherosclerosis (mean age 34.5 ± 11.8 years, p < 0.002). Two mummies had evidence of severe arterial atherosclerosis with calcifications in virtually every arterial bed. Definite coronary atherosclerosis was present in 2 mummies, including a princess who lived between 1550 and 1580 BCE. This finding represents the earliest documentation of coronary atherosclerosis in a human. Definite or probable atherosclerosis was present in mummies who lived during virtually every era of ancient Egypt represented in this study, a time span of >2,000 years.

CONCLUSIONS: Atherosclerosis is commonplace in mummified ancient Egyptians.

PMID: 21466986

LV Mechanical Dyssynchrony in Heart Failure With Preserved Ejection Fraction Complicating Acute Coronary Syndrome

OBJECTIVES: The aim of this study was to evaluate the role of left ventricular (LV) mechanical dyssynchrony in heart failure with preserved ejection fraction (HFPEF) complicating acute coronary syndrome (ACS). In systolic heart failure, LV mechanical dyssynchrony worsens cardiac function and cardiac resynchronization therapy improves clinical outcome. The role of LV mechanical dyssynchrony in HFPEF complicating ACS is unknown.

METHODS: One hundred two patients presenting with ACS (ejection fraction ≥50%) and 104 healthy controls were studied using tissue Doppler imaging: group 1 (n = 55) had HFPEF on presentation and group 2 (n = 47) had no clinical HFPEF. The SD of time to peak systolic myocardial velocity and the SD of early diastolic (Te-SD) myocardial velocity of 12 LV segments were obtained for evaluation of dyssynchrony. Longitudinal mean myocardial ejection systolic velocity (mean Sm) and mean early diastolic velocity (mean Em) were measured.

RESULTS: Te-SD was greater in group 1 (33 ± 13 ms) than group 2 (21 ± 9 ms) (p < 0.001), and diastolic mechanical dyssynchrony was evident in 35% of patients in group 1 but in only 9% in group 2 (p < 0.001). Conversely, the SD of time to peak systolic myocardial velocity was similar in the 2 ACS groups (34 ± 16 ms vs. 32 ± 18 ms; p = NS), showing a similar prevalence of systolic mechanical dyssynchrony (47% vs. 43%; p = NS). Worsening of the diastolic dysfunction grade was associated with a parallel increase in Te-SD (grades 0, 1, 2, and 3: 16 ± 3 ms, 21 ± 5 ms, 28 ± 9 ms, and 41 ± 17 ms, respectively; p < 0.001). Te-SD correlated negatively with mean Em (r = -0.56, p < 0.001) and positively with peak mitral inflow velocity of the early rapid-filling wave/Em (r = 0.69, p < 0.001); mean myocardial ejection systolic velocity correlated significantly with mean Em (r = 0.56, p < 0.001), SD of time to peak systolic myocardial velocity (r = -0.42, p < 0.001) and Te-SD (r = -0.23, p = 0.001). Multivariate analysis identified peak mitral inflow velocity of the early rapid-filling wave/Em as the only variable independently associated with HFPEF (odds ratio: 1.48, p = 0.001). When peak mitral inflow velocity of the early rapid-filling wave/Em was excluded from the model, Te-SD (odds ratio: 1.13, p < 0.001) and mean Em (odds ratio: 0.37, p < 0.001) became independently associated with HFPEF.

CONCLUSIONS: LV diastolic mechanical dyssynchrony may impair diastolic function and contribute to the pathophysiology of HFPEF, complicating ACS

PMID: 21492809

Dependency of Cardiac Resynchronization Therapy on Myocardial Viability at the LV Lead Position

OBJECTIVES: This study sought to analyze the effectiveness of cardiac resynchronization therapy (CRT) related to the viability in the segment of left ventricular (LV) lead position defined by myocardial deformation imaging. Echocardiographic myocardial deformation analysis allows determination of LV lead position as well as extent of myocardial viability.

METHODS: Myocardial deformation imaging based on tracking of acoustic markers within 2-dimensional echo images (GE Ultrasound, GE Healthcare, Horton, Norway) was performed in 65 heart failure patients (54 ± 6 years of age, 41 men) before and 12 months after CRT implantation. In a 16-segment model, the LV lead position was defined based on the segmental strain curve with earliest peak strain, whereas the CRT system was programmed to pure LV pacing. Non-viability of a segment (transmural scar formation) was assumed if the peak systolic circumferential strain was >-11.1%.

RESULTS: In 47 patients, the LV lead was placed in a viable segment, and in 18 patients, it was placed in a nonviable segment. At 12-month follow-up there was greater decrease of LV end-diastolic volumes (58 ± 13 ml vs. 44 ± 12 ml, p = 0.0388) and greater increase of LV ejection fraction (11 ± 4% vs. 5 ± 4%, p = 0.0343) and peak oxygen consumption (2.5 ± 0.9 ml/kg/min vs. 1.7 ± 1.1 ml/kg/min, p = 0.0465) in the viable compared with the nonviable group. The change in LV ejection fraction and the reduction in LV end-diastolic volumes at follow-up correlated to an increasing peak systolic circumferential strain in the segment of the LV pacing lead (r = 0.61, p = 0.0274 and r = 0.64, p = 0.0412, respectively). Considering only patients with ischemic heart disease, differences between viable and nonviable LV lead position group were even greater.

CONCLUSIONS: Preserved viability in the segment of the CRT LV lead position results in greater LV reverse remodeling and functional benefit at 12-month follow-up. Deformation imaging allows analysis of viability in the LV lead segment.

PMID: 21492811

Features of Disrupted Plaques by Coronary Computed Tomographic Angiography: Correlates With Invasively Proven Complex Lesions

PMID: 21262981

Epicardial Fat: An Additional Measurement for Subclinical Atherosclerosis and Cardiovascular Risk Stratification?

OBJECTIVES:  The value of epicardial adipose tissue (EAT) thickness as determined by echocardiography in cardiovascular risk assessment is not well understood. The aim of this study was to determine the associations between EAT thickness and Framingham risk score, carotid intima media thickness, carotid artery plaque, and computed tomographic coronary calcium score in a primary prevention population.

METHODS:  Patients presenting for cardiovascular preventive care (n = 356) who underwent echocardiography as well as carotid artery ultrasound and/or coronary calcium scoring were included.

RESULTS:  EAT thickness was weakly correlated with Framingham risk score. The prevalence of carotid plaque was significantly greater in those with EAT thickness ≥5.0 mm who either had low Framingham risk scores or had body mass indexes ≥25 kg/m(2), compared with those with EAT thickness <5.0 mm. No significant association between EAT thickness and carotid intima-media thickness or coronary calcium score existed.

CONCLUSIONS:  EAT thickness ≥5.0 mm may identify an individual with a higher likelihood of having detectable carotid atherosclerosis.

PMID: 21185148