Claudia E. Korcarz

Serial Assessment of the Cardiovascular System in Normal Pregnancy Role of Arterial Compliance and Pulsatile Arterial Load

BACKGROUND Temporal changes in systemic arterial compliance and wave propagation properties (pulsatile arterial load) and their role in ventricular-systemic arterial coupling during gestation have not been explored. Noninvasive methods combined with recently developed mathematical modeling techniques were used to characterize vascular and left ventricular (LV) mechanical adaptations during normal gestation. METHODS AND RESULTS Fourteen healthy women were studied at each trimester of pregnancy and again postpartum. Experimental measurements included instantaneous aortic pressure (subclavian pulse tracings) and flow (aortic Doppler velocities) and echocardiographic imaging of the LV. A small increase in LV muscle mass and end-diastolic chamber dimension occurred by late gestation, with no significant alterations in myocardial contractility. Cardiac output increased and the steady component of arterial load (total vascular resistance) decreased during pregnancy. Several changes in pulsatile arterial load were noted: Global arterial compliance increased (approximately 30%) during the first trimester and remained elevated thereafter. The magnitude of peripheral wave reflections at the aorta was reduced. The mathematical model-based analysis revealed that peripheral wave reflections at the aorta were delayed and that both conduit and peripheral vessels contributed to the increased arterial compliance. Finally, coordinated changes in the pulsatile arterial load and LV properties were responsible for maintaining the efficiency of LV-to-arterial system energy transfer. CONCLUSIONS The rapid time course of compliance changes and the involvement of both conduit and peripheral vessels are consistent with reduced vascular tone as being the main underlying mechanism. The pulsatile arterial load alterations during normal pregnancy are adaptive in that they help to accommodate the increased intravascular volume while maintaining the efficiency of ventricular-arterial coupling and diastolic perfusion pressure.

Focused Cardiac Ultrasound: Recommendations from the American Society of Echocardiography

1. Why is a guideline needed? 567 2. Definitions 568 a. What is FCU? 568 b. Terminology 568 3. Differentiation of FCU and ‘‘Limited TTE’’ 568 a. Examination Expectations 569 b. Equipment 570 c. Image Acquisition 570 d. Image Interpretation 570 e. Billing 571 4. Considerations for Successful Use of FCU as an Adjunct to Physical Examination 571 a. Personnel 571 b. Equipment 571 c. Potential Limitations of FCU 572 5. FCU Scope of Practice 573 a. FCU When Echocardiography is Not Promptly Available 573 b. FCU When Echocardiography is Not Practical 574

Echocardiographic Quantification of Regional Left Ventricular Wall Motion With Color Kinesis

BACKGROUND Color kinesis is a new technology for the echocardiographic assessment of left ventricular wall motion based on acoustic quantification. This technique automatically detects endocardial motion in real time by using integrated backscatter data to identify pixel transitions from blood to tissue during systole on a frame-by-frame basis. In this study, we evaluated the feasibility and accuracy of quantitative segmental analysis of color kinesis images to provide objective evaluation of regional systolic endocardial motion. METHODS AND RESULTS Two-dimensional echocardiograms were obtained in the short-axis and apical four-chamber views in 20 normal subjects and 40 patients with regional wall motion abnormalities. End-systolic color overlays superimposed on the gray scale images were obtained with color kinesis to color encode left ventricular endocardial motion throughout systole on a frame-by-frame basis. These color-encoded images were divided into segments by use of custom software. In each segment, pixels of different colors were counted and displayed as stacked histograms reflecting the magnitude and timing of regional endocardial excursion. In normal subjects, histograms were found to be highly consistent and reproducible. The patterns of contraction obtained in normal subjects were used as a reference for the objective automated interpretation of regional wall motion abnormalities, defined as deviations from this pattern. The variability in the echocardiographic interpretation of wall motion between two experienced readers was similar to the diagnostic variability between the consensus of the two readers and the automated interpretation. CONCLUSIONS Color kinesis is a promising new tool that may be used clinically to improve the qualitative and quantitative evaluation of spatial and temporal aspects of global and regional wall motion. In this initial study, segmental analysis of color kinesis images provided accurate, automated, and quantitative diagnosis of regional wall motion abnormalities.

Use of harmonic imaging without echocardiographic contrast to improve two-dimensional image quality.

The aim of this study was to determine whether harmonic imaging (HI) improves endocardial visualization during 2-dimensional echocardiography without echocardiographic contrast. HI differs from fundamental imaging (FI) by transmitting ultrasound at one frequency and receiving at twice the transmitted frequency. This technique has been used in conjunction with contrast echocardiography to enhance myocardial contrast visualization. HI and FI were sequentially performed in 20 patients. Images were digitally stored and subsequently reviewed by 2 observers for the quality of endocardial visualization. In addition, acoustic quantification was performed in both FI and HI modes and endocardial tracking qualitatively judged. HI was compared with FI during dobutamine stress echocardiography in 17 patients who were imaged at baseline and peak stress. Overall, the harmonic images had less clutter and better myocardial blood contrast. Individual segments were better visualized with HI in 30% to 73% of cases. The acoustic quantification endocardial tracking was rated better with HI in 67% of short-axis views and in 58% of apical 4-chamber views. During dobutamine stress testing the overall number of interpretable segments improved from 64% for FI to 84% with HI. Many segments traditionally difficult to image were improved with HI. HI without the use of contrast agents improved endocardial visualization during routine 2-dimensional echocardiography. This improved endocardial visualization led to better endocardial tracking with acoustic quantification and to more segments being clinically interpretable during dobutamine stress testing.

A Prospective Randomized Controlled Trial of the Effects of Vitamin D Supplementation on Cardiovascular Disease Risk

Vitamin D (VitD) supplementation has been advocated for cardiovascular risk reduction; however, supporting data are sparse. The objective of this study was to determine whether VitD supplementation reduces cardiovascular risk. Subjects in this prospective, randomized, double-blind, placebo-controlled trial of post-menopausal women with serum 25-hydroxyvitamin D concentrations >10 and <60 ng/mL were randomized to Vitamin D3 2500 IU or placebo, daily for 4 months. Primary endpoints were changes in brachial artery flow-mediated vasodilation (FMD), carotid-femoral pulse wave velocity (PWV), and aortic augmentation index (AIx). The 114 subjects were mean (standard deviation) 63.9 (3.0) years old with a 25-hydroxyvitamin D level of 31.3 (10.6) ng/mL. Low VitD (<30 ng/mL) was present in 47% and was associated with higher body-mass index, systolic blood pressure, glucose, CRP, and lower FMD (all p<0.05). After 4 months, 25-hydroxyvitamin D levels increased by 15.7 (9.3) ng/mL on vitamin D3 vs. −0.2 (6.1) ng/mL on placebo (p<0.001). There were no significant differences between groups in changes in FMD (0.3 [3.4] vs. 0.3 [2.6] %, p = 0.77), PWV (0.00 [1.06] vs. 0.05 [0.92] m/s, p = 0.65), AIx (2.7 [6.3] vs. 0.9 [5.6] %, p = 0.10), or CRP (0.3 [1.9] vs. 0.3 [4.2] mg/L, p = 0.97). Multivariable models showed no significant interactions between treatment group and low VitD status (<30 ng/mL) for changes in FMD (p = 0.65), PWV (p = 0.93), AIx (p = 0.97), or CRP (p = 0.26).In conclusion, VitD supplementation did not improve endothelial function, arterial stiffness, or inflammation. These observations do not support use of VitD supplementation to reduce cardiovascular disease risk. Trial Registration ClinicalTrials.gov NCT00690417 Trial Registration ClinicalTrials.gov NCT01049048

Combined Assessment of Myocardial Perfusion and Regional Left Ventricular Function by Analysis of Contrast-Enhanced Power Modulation Images

Background—Echocardiographic contrast media have been used to assess myocardial perfusion and to enhance endocardial definition for improved assessment of left ventricular (LV) function. These methodologies, however, have been qualitative or have required extensive offline image analysis. Power modulation is a recently developed imaging technique that provides selective enhancement of microbubble-generated reflections. Our goal was to test the feasibility of using power modulation for combined quantitative assessment of myocardial perfusion and regional LV function in an animal model of acute ischemia. Methods and Results—Coronary balloon occlusions were performed in 18 anesthetized pigs. Transthoracic power modulation images (Agilent 5500) were obtained during continuous intravenous infusion of the contrast agent Definity (DuPont) at baseline and during brief coronary occlusion and reperfusion and were analyzed with custom software. At each phase, myocardial perfusion was assessed by calculation, in 6 myocardial regions of interest, of mean pixel intensity and the rate of contrast replenishment after high-power ultrasound impulses. LV function was assessed by calculation of regional fractional area change from semiautomatically detected endocardial borders. All ischemic episodes caused detectable and reversible changes in perfusion and function. Perfusion defects, validated with fluorescent microspheres, were visualized in real time and confirmed by a significant decrease in pixel intensity in the left anterior descending coronary artery territory after balloon inflation and reduced rate of contrast replenishment. Fractional area change decreased significantly in ischemic segments and was restored with reperfusion. Conclusions—Power modulation allows simultaneous online assessment of myocardial perfusion and regional LV wall motion, which may improve the echocardiographic diagnosis of myocardial ischemia.

Effects of smoking and smoking cessation on endothelial function: 1-year outcomes from a randomized clinical trial.

OBJECTIVES The purpose of this study was to determine whether smoking cessation improves flow-mediated dilation (FMD) of the brachial artery. BACKGROUND The long-term effects of continued smoking and smoking cessation on endothelial function have not been described previously. METHODS This was a 1-year, prospective, double-blind, randomized, placebo-controlled clinical trial of the effects of 5 smoking cessation pharmacotherapies. FMD was measured by B-mode ultrasonography before and 1 year after the target smoking cessation date. Cessation was verified by exhaled carbon monoxide levels. DeltaFMD was compared among study arms and between subjects who successfully quit smoking and those who continued to smoke. Predictors of baseline FMD and DeltaFMD were identified by multivariable regression. RESULTS The 1,504 current smokers (58% female, 84% white) were 44.7 +/- 11.1 years of age and smoked 21.4 +/- 8.9 cigarettes/day. Baseline FMD was similar in each treatment arm (p = 0.499) and was predicted by BA diameter (p < 0.001), reactive hyperemia blood flow (p < 0.001), high-density lipoprotein cholesterol (p = 0.001), and carbon monoxide (p = 0.012) levels. After 1 year, 36.2% quit smoking. FMD increased by 1% (6.2 +/- 4.4% to 7.2 +/- 4.2%) after 1 year (p = 0.005) in those who quit, but did not change (p = 0.643) in those who continued to smoke. Improved FMD among quitters remained significant (p = 0.010) after controlling for changes in brachial artery diameter, reactive hyperemia, low-density lipoprotein cholesterol, and the presence of a home smoking ban. CONCLUSIONS Despite weight gain, smoking cessation leads to prolonged improvements in endothelial function, which may mediate part of the reduced cardiovascular disease risk observed after smoking cessation. (Smoking Cessation Medications: Efficacy, Mechanisms and Algorithms; NCT00332644).

Objective Evaluation of Regional Left Ventricular Wall Motion During Dobutamine Stress Echocardiographic Studies Using Segmental Analysis of Color Kinesis Images

OBJECTIVES To test the feasibility of objective and automated evaluation of echocardiographic stress tests, we studied the ability of segmental analysis of color kinesis (CK) images to detect dobutamine-induced wall motion abnormalities and compared this technique with inexperienced reviewers of conventional gray-scale images. BACKGROUND Conventional interpretation of stress echocardiographic studies is subjective and experience dependent. METHODS CK images were obtained in 89 of 104 consecutive patients undergoing clinical dobutamine stress studies and were analyzed using custom software to calculate regional fractional area change in 22 segments in four standard views. Each patients data obtained at rest was used as a control for automated detection of dobutamine-induced wall motion abnormalities. Independently, studies were reviewed without CK overlays by two inexperienced readers who classified each segments response to dobutamine. A consensus reading of two experienced reviewers was used as the gold standard for comparisons. In a subgroup of 16 patients, these consensus readings and CK detection of wall motion abnormalities were compared with coronary angiography. RESULTS The consensus reading detected ischemic response to dobutamine in 43 of 1958 segments in 23 of 89 patients. Automated detection of stress-induced wall motion abnormalities correlated more closely with the standard technique than the inexperienced reviewers (sensitivity 0.76 vs. 0.55, specificity 0.98 vs. 0.94 and accuracy 0.97 vs. 0.92). When compared with coronary angiography in a subgroup of patients, analysis of CK images differentiated between normal and abnormal wall motion more accurately than expert readers of gray-scale images (accuracy of 0.93 vs. 0.82). CONCLUSIONS Analysis of CK images allows fast, objective and automated evaluation of regional wall motion, sensitive enough for clinical dobutamine stress data and more accurate than inexperienced readers. This method may result in a valuable adjunct to conventional visual interpretation of dobutamine stress echocardiography.

Noninvasive method for determination of arterial compliance using Doppler echocardiography and subclavian pulse tracings. Validation and clinical application of a physiological model of the circulation.

BACKGROUND The Poiseuillian model of the arterial system currently applied in clinical physiology does not explain how arterial pressure is maintained during diastole after cessation of pulsatile aortic inflow. Arterial pressure-flow relations can be more accurately described by models that incorporate arterial viscoelastic properties such as arterial compliance. Continuous pressure and flow measurements are needed to evaluate these properties. Since the techniques used to date to acquire such data have been invasive, physiological models of the circulation that incorporate these properties have not been widely applied in the clinical setting. The purpose of this study was (1) to validate noninvasive methods for continuous measurement of central arterial pressure and flow and (2) to determine normal reference values for arterial compliance using physiological models of the circulation applied to the noninvasively acquired pressure and flow data. METHODS AND RESULTS Simultaneously acquired invasive and noninvasive aortic pressures (30 patients), flows (8 patients), and arterial mechanical properties (8 patients) were compared. Pressure was measured by high-fidelity catheter aortic micromanometer (invasive) and calibrated subclavian pulse tracing (noninvasive). Aortic inflow was determined from thermodilution-calibrated electromagnetic flow velocity data (invasive) and echo-Doppler data (noninvasive). Arterial compliance was determined for two- and three-element windkessel models of the circulation using the area method and an iterative procedure, respectively. Once validated, the noninvasive methodology was used to determine normal compliance values for a reference population of 70 subjects (age range, 20 to 81 years) with normal 24-hour ambulatory blood pressures and without Doppler-echocardiographic evidence for structural heart disease. The limits of agreement between invasive and noninvasive pressure data, compared at 10% intervals during ejection and nonejection, were narrow over a wide range of pressures, with no significant differences between methods. Invasive and noninvasive instantaneous aortic inflow values differed slightly but significantly at the start of ejection (P < .05), but during the latter 90% of ejection, values for the two methods were similar, with narrow limits of agreement. Total vascular resistance and arterial compliance values derived from invasive and noninvasive data were similar. Arterial compliance values for the normal population using the two-element model (C2E) ranged from 0.74 to 2.44 cm3/mm Hg (mean, 1.57 +/- 0.38 cm3/mm Hg), with a beat-to-beat variability of 5.2 +/- 3.9%. C2E decreased with increasing age (r = -.73, P < .001) and tended to be higher in men (1.67 +/- 0.41 cm3/mm Hg) than in women (1.51 +/- 0.35 cm3/mm Hg, P = .07). Compliance values for the three-element model (C3E) were predictably smaller than for the two-element model (mean, 1.23 +/- 0.30; range, 0.59 to 2.16 cm3/mm Hg, P < .001 versus C2E) but correlated with C2E values (r = .81, P < .001) and were also inversely related to age (r = -.56, P < .001). Ridge regression and principal component analyses both showed the compliance value to be a composite function whose variation could be best predicted by consideration of simultaneous values for five major hemodynamic determinants: heart rate, mean flow, mean aortic pressure, minimal diastolic pressure, and end-systolic pressure. Multivariate analysis revealed age and sex to be independent predictors of compliance (P < .01 for both). There were no differences in compliance between black and white subjects. CONCLUSIONS Noninvasive methods can be used to acquire the hemodynamic data necessary for clinical application of physiological models of the circulation that incorporate arterial viscoelastic properties such as arterial compliance. The strong inverse linear relation between model-based compliance estimates and age mandates incorporation of this demographic parameter in

Predictors of Carotid Thickness and Plaque Progression During a Decade: The Multi-Ethnic Study of Atherosclerosis

Background and Purpose— Carotid artery intima-media thickness (IMT) and plaque are noninvasive markers of subclinical arterial injury that predict incident cardiovascular disease. We evaluated predictors of longitudinal changes in IMT and new plaque during a decade in a longitudinal multiethnic cohort. Methods— Carotid IMT and plaque were evaluated in Multi-Ethnic Study of Atherosclerosis (MESA) participants at exams 1 and 5, a mean (standard deviation) of 9.4 (0.5) years later. Far wall carotid IMT was measured in both common and internal carotid arteries. A plaque score was calculated from all carotid segments. Mixed-effects longitudinal and multivariate regression models evaluated associations of baseline risk factors and time-updated medication use with IMT progression and plaque formation. Results— The 3441 MESA participants were aged 60.3 (9.4) years (53% women; 26% blacks, 22% Hispanic, 13% Chinese); 1620 (47%) had carotid plaque. Mean common carotid artery IMT progression was 11.8 (12.8) &mgr;m/year, and 1923 (56%) subjects developed new plaque. IMT progressed more slowly in Chinese (&bgr;=−2.89; P=0.001) and Hispanic participants (&bgr;=−1.81; P=0.02), and with higher baseline high-density lipoprotein cholesterol (per 5 mg/dL; &bgr;=−0.22; P=0.03), antihypertensive use (&bgr;=−2.06; P=0.0004), and time on antihypertensive medications (years; &bgr;=−0.29; P<0.0001). Traditional risk factors were associated with new plaque formation, with strong associations for cigarette use (odds ratio, 2.31; P<0.0001) and protection by black ethnicity (odds ratio, 0.68; P<0.0001). Conclusions— In a large, multiethnic cohort with a decade of follow-up, ethnicity was a strong, independent predictor of carotid IMT and plaque progression. Antihypertensive medication use was associated with less subclinical disease progression.