Introduction: Vasodilation can paradoxically increase arterial stiffness in older, hypertensive a... more Introduction: Vasodilation can paradoxically increase arterial stiffness in older, hypertensive adults. This study modeled increasing smooth muscle tone as a therapeutic strategy to improve central arterial dysfunction in hypertension using participant-specific simulations. Methods: Participant-specific models of the carotid artery were parameterized from vascular ultrasound measures of nitroglycerin-induced vasodilation in 18 hypertensive veterans. The acute changes in carotid artery mechanics were simulated for changes of ±2, ±4, and ±6% in smooth muscle tone and ±5, ±10, and ±15 mmHg in mean arterial pressure (MAP). The chronic carotid artery adaptations were simulated based on the hypothesis that the carotid artery will remodel wall-cross sectional area to maintain mechanical homeostasis. Results: A 6% increase in smooth muscle tone acutely decreased carotid pulse wave velocity from 6.89 ± 1.24 m/s to 5.83 ± 1.73 m/s, and a 15 mmHg decrease in MAP decreased carotid pulse wave velocity to 6.17 ± 1.23 m/s. A 6% increase in smooth muscle tone acutely decreased wall stress from 76.2 ± 12.3 to 64.2 ± 10.4 kPa, and a 15 mmHg decrease in MAP decreased wall stress to 60.6 ± 10.7 kPa. A 6% increase in smooth muscle tone chronically decreased wall cross-sectional area from 18.3 ± 5.4 to 15.2 ± 4.9 mm2, and a 15 mmHg decrease in MAP decreased wall cross-sectional area to 14.3 ± 4.6 mm2. Conclusion: In participant-specific simulation, increasing smooth muscle tone can have a stronger or equivalent effect on carotid artery mechanics compared with decreasing blood pressure. Increasing central arterial smooth muscle tone may be a novel therapeutic target to improve central arterial dysfunction in older, hypertensive adults and should be a focus of future research.
Background: Elastic arteries stiffen via 2 main mechanisms: (1) load-dependent stiffening from hi... more Background: Elastic arteries stiffen via 2 main mechanisms: (1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to changes in the vessel wall. It is unknown how these different mechanisms contribute to incident cardiovascular disease (CVD) events. Methods: The MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study of 6814 men and women without CVD at enrollment, from 6 communities in the United States. MESA participants with B-mode carotid ultrasound and brachial blood pressure at baseline Exam in (2000–2002) and CVD surveillance (mean follow-up 14.3 years through 2018) were included (n=5873). Peterson’s elastic modulus was calculated to represent total arterial stiffness. Structural stiffness was calculated by adjusting Peterson’s elastic modulus to a standard blood pressure of 120/80 mm Hg with participant-specific models. Load-dependent stiffness was the difference between total and structural stiffness. Results: In Cox models adjusted for traditional risk factors, load-dependent stiffness was significantly associated with higher incidence of CVD events (hazard ratio/100 mm Hg, 1.21 [95% CI, 1.09–1.34] P <0.001) events while higher structural stiffness was not (hazard ratio, 1.03 [95% CI, 0.99–1.07] P =0.10). Analysis of participants who were normotensive (blood pressure <130/80, no antihypertensives) at baseline exam (n=2122) found higher load-dependent stiffness was also associated with significantly higher incidence of hypertension (hazard ratio, 1.53 [95% CI, 1.35–1.75] P <0.001) while higher structural stiffness was not (hazard ratio, 1.03 [95% CI, 0.99–1.07] P =0.16). Conclusions: These results provide valuable new insights into mechanisms underlying the association between arterial stiffness and CVD. Load-dependent stiffness was significantly associated with CVD events but structural stiffness was not.
Journal of The American Society of Echocardiography, Feb 1, 2002
There is no method to objectively evaluate left ventricular (LV) function from contrast-enhanced ... more There is no method to objectively evaluate left ventricular (LV) function from contrast-enhanced images. We tested the feasibility of evaluating regional LV function by using power modulation imaging. In protocol 1, 9 anesthetized closed-chest pigs were studied. Images were obtained during contrast infusion at baseline, during LAD occlusion and reperfusion. In protocol 2, images were obtained in 20 patients (14 wall-motion abnormalities; 6 controls) during contrast enhancement. Off-line, frame-by-frame, semiautomated endocardial border detection was followed by color encoding of endocardial motion, followed by segmentation and calculation of regional fractional area changes. In all animals, coronary occlusions resulted in hypokinesis and decreased fractional area changes in LAD-related segments only, which were reversed during reperfusion. In patients, wall-motion analysis was in agreement with an expert reader of dynamic images in 92.5% segments, with interobserver variability of 12.5%. Color encoding of endocardial motion from contrast-enhanced power modulation images allows accurate quantitative assessment of regional LV function.
Background and PurposeMany health effects of sleep apnea (SA) may be mediated through accelerated... more Background and PurposeMany health effects of sleep apnea (SA) may be mediated through accelerated atherosclerosis. We examined the associations of snoring and several measurements of SA with subclinical carotid atherosclerosis in a large multiethnic population sample.MethodsThis analysis included 1615 participants (mean age 68 years) from examination 5 (2010-2013) of the Multi-Ethnic Study of Atherosclerosis. Sleep measures including SA (apnea-hypopnea index [AHI 4%] ≥15 events/hour) were derived from full in-home polysomnography. Carotid atherosclerosis was measured using high-resolution B-mode ultrasound. Multivariable linear and logistic regression models were used to evaluate the associations between sleep exposures with carotid intima-media thickness (CIMT) and the presence of carotid plaque, respectively. Effect modification by age, sex, and race/ethnicity was examined.ResultsIn multivariable analysis, SA was associated with an increased odds of carotid plaque presence in individuals aged <68 years (odds ratio [OR], 1.47; 95% confidence interval [CI] 1.05 to 2.06) but not in older individuals (OR 0.95; 95% CI 0.67 to 1.37, p-interaction=0.078). Greater hypoxemia (sleep time <90% saturation) was associated with increasing CIMT in younger (0.028 ± 0.014 mm) but not in older individuals (−0.001 ± 0.013 mm, p-interaction= 0.106). Self-reported snoring was not associated with carotid atherosclerosis. In assessing race-specific outcomes, greater hypoxemia was associated with increased CIMT in Blacks (0.049 ±0.017 mm, p-interaction=0.033).ConclusionsIn this large multiethnic population-based sample, sleep disturbances are associated with subclinical carotid atherosclerosis in both men and women, particularly in those <68 years. The mechanisms underlying the association between sleep apnea and carotid atherosclerosis may differ for carotid plaque and CIMT.
Background Color kinesis is a new technology for the echocardiographic assessment of left ventric... more 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.
Objectives: In pulmonary hypertension associated with HFpEF (PH-HFpEF), identifying mechanisms of... more Objectives: In pulmonary hypertension associated with HFpEF (PH-HFpEF), identifying mechanisms of right ventricular: pulmonary arterial (RV:PA) uncoupling can be leveraged for sub-phenotyping and targeted therapies. In this study, we aim to distinguish mechanisms of RV:PA uncoupling in PH-HFpEF due to high RV afterload (afterload-sensitive; AS) and impaired left ventricular-interventricular septal contributions to RV function (ventricular interdependence; VI). Methods: Subjects (n=13) with early-stage PH (per echo) and NYHA II-III dyspnea were prospectively enrolled. Exclusion criteria: advanced disease with NYHA IV, LVEF &lt;50%. All subjects underwent rest-to-exercise (every 25 watts) invasive cardiopulmonary exercise test and echo (for impedance: characteristic for pulsatile load Z C , input for steady load Z 0 ), followed by RV real-time pressure volume (PV)-loops. Subsequently, a cardiac MRI was performed with temporal resolution of 25-30 msec. Five study subjects had isolated post-capillary (Ipc-PH), 5 had pulmonary arterial hypertension, 2 had combined pre/post-capillary PH, and 1 had no PH. Results: With exercise, impedance (Z C and Z 0 ) increased or remained unchanged in all PH subjects but decreased in the subject with no PH. Z C (time domain method) was correlated with PV-loop based uncoupling (end-systolic to elastance ratio Ees:Ea) among Ipc-PH subjects (r 2 =0.40, p&lt;0.01), but had poor correlation in other phenotypes (r2=0.01, p=0.11). As next step, within each IpcPH subject, correlation of Z C with Ees:Ea (with repeated measures across exercise stages) was determined to identify afterload sensitivity (Figure). Cardiac MRI-based regional strain was used to identify ventricular interdependence; defined as reduced strain of interventricular septum (Figure). Conclusions: Multimodality methods to assess RV:PA uncoupling in PH-HFpEF can identify afterload-sensitive phenotypes, which may benefit from focused interventions.
Background: The acute cardiovascular effects of electronic nicotine delivery devices (ENDs) have ... more Background: The acute cardiovascular effects of electronic nicotine delivery devices (ENDs) have not been well-characterized. We hypothesized differences in acute cardiovascular and autonomic function responses to use of ENDS by chronic ENDs users (“vapers”), use of combustible cigarettes by chronic “smokers,” and no product use among non-smoking/non-vaping controls. Methods: CLUES (HL1393301) was a cross-sectional study of 395 individuals: 164 exclusive vapers (exhaled carbon monoxide [CO] &lt;5 ppm, positive urine NicCheck I test), 117 exclusive smokers (CO &gt;5 ppm, positive urine NicCheck), and 114 non-vaping/non-smoking controls (CO &lt;5 ppm, negative urine NicCheck). We measured systolic and diastolic blood pressure (BP), heart rate (HR), brachial artery diameter, and time domain HR variability (root mean square differences in successive normal intervals [RMSSD]; % adjacent normal intervals &gt;50 ms [PNN50]) before and 15’ after a product use challenge. Linear mixed models were created to predict outcome measures from group, time, and group*time with age, sex, and race as covariates, followed by group contrasts via post-hoc t-tests with Bonferroni-corrected p values. Results: Vapers were a mean (SD) 27.4 (10.6) years old (39% female, 86% white) and had vaped for 4.1 (2.7) years. Smokers were 42.8 (13.8) years old (44% female, 56% white) and had smoked for 23.0 (13.0) years. Controls were 30.8 (11.9) years old (50% female, 69% white). Model-adjusted mean (95% CIs) outcomes and p values for between group differences in challenge responses are in the Figure. Compared to controls, vapers had greater increases in systolic BP, diastolic BP, and HR (all p &lt; 0.002) and greater reductions in brachial artery diameter, RMSSD, and PNN50 (all p &lt; 0.003) than controls, with values similar to smokers. Conclusion: Chronic vapers showed acute increases in BP and HR, vasoconstriction, and reductions in time domain HR variability after using ENDS, similar to cigarette use by smokers.
Introduction: Stiff arteries increase the risk of end organ damage to the brain and kidneys. Arte... more Introduction: Stiff arteries increase the risk of end organ damage to the brain and kidneys. Arterial stiffness can be separated into two main mechanisms: 1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to remodeling of the vessel wall. The relationship between arterial stiffness mechanisms and end organ damage risk is unknown. Hypothesis: Both stiffness mechanisms will be significantly associated with chronic kidney disease (CKD), dementia, and mortality. Methods: MESA participants with B-mode carotid ultrasound in 2000-2002 were included in this study (n=6147). Carotid pulse wave velocity (cPWV) was calculated to represent total stiffness. Structural stiffness was calculated by adjusting cPWV to a 120/80 BP with participant-specific models. Load dependent (LD) stiffness was the difference of total and structural stiffness. Associations with incident CKD, dementia defined by ICD codes, and mortality were assessed with Cox models adjusted for age, sex, race/ethnicity, education, study site, smoking, pack-years, diabetes, BMI, SBP, non-HDL-C, BP medication, and lipid medication. Results: During 14.3±4.8 years of follow-up, 773 CKD events, 535 dementia events, and 1529 deaths occurred. Total cPWV was associated with mortality (HR 1.04 [1.01-1.08], p=0.02) and dementia (HR 1.06 [1.01 - 1.12], p=0.03). Structural cPWV was significantly associated with mortality (HR 1.04 [1.00 - 1.08], p=0.04) but not CKD (HR 1.00 [0.94-1.05], p=0.86) or dementia (HR 1.06 [0.99-1.13], p=0.06). LD cPWV was associated with CKD (HR 1.38 [1.17 - 1.63], p&lt;0.001) but not mortality (HR 1.11 [0.99-1.25], p=0.07) or dementia (HR 1.14 [0.94-1.38], p=0.19). Conclusions: Structural carotid artery stiffness was significantly associated with all-cause mortality, while LD stiffness was significantly associated with CKD. Total carotid stiffness was associated with incident dementia but LD and structural stiffness mechanisms were not.
Journal of the American Heart Association, Apr 4, 2023
Background Arterial stiffness can be separated into 2 main mechanisms: (1) load‐dependent stiffen... more Background Arterial stiffness can be separated into 2 main mechanisms: (1) load‐dependent stiffening from higher blood pressure and (2) structural stiffening due to remodeling of the vessel wall. The relationship between stiffness mechanisms and end organ damage is unknown. Methods and Results MESA (Multi‐Ethnic Study of Atherosclerosis) participants with carotid ultrasound were included in this study (n=6147). Carotid pulse wave velocity (cPWV) was calculated to represent total stiffness. Structural stiffness was calculated by adjusting cPWV to a 120/80 mm Hg blood pressure with participant‐specific models. Load‐dependent stiffness was the difference of total and structural stiffness. Associations with incident chronic kidney disease (CKD), dementia, and mortality were assessed with adjusted Cox models. During 14.3±4.8 years of follow‐up, 773 CKD events, 535 dementia events, and 1529 deaths occurred. Total cPWV was associated with mortality (hazard ratio [HR], per 1 m/s, 1.04 [95% CI, 1.01–1.08], P =0.02) and dementia (HR, 1.06 [95% CI, 1.01–1.12], P =0.03) but not CKD (HR, 1.03 [95% CI, 0.98–1.08], P =0.33). Structural cPWV was significantly associated with mortality (HR, 1.04 [95% CI, 1.00–1.08], P =0.04) but not CKD (HR, 1.00 [95% CI, 0.94–1.05], P =0.86) or dementia (HR, 1.06 [95% CI, 0.99–1.13], P =0.06). Load‐dependent cPWV was significantly associated with CKD (HR, 1.38 [95% CI, 1.17–1.63], P &lt;0.001) but not mortality (HR, 1.11 [95% CI, 0.99–1.25], P =0.07) or dementia (HR, 1.14 [95% CI, 0.94–1.38], P =0.19). Conclusions The mechanisms of arterial stiffness were associated with all‐cause mortality and CKD. Structural stiffness was associated with all‐cause mortality, and load‐dependent stiffness was associated with CKD. Total stiffness was associated with dementia but load‐dependent and structural stiffness were not.
Journal of The American Society of Echocardiography, Feb 1, 2003
Quantitative analysis of myocardial perfusion is currently based on manual tracing and frame-by-f... more Quantitative analysis of myocardial perfusion is currently based on manual tracing and frame-by-frame realignment of regions of interest. We developed a technique for semiautomated identification of myocardial regions from power modulation images as a potential tool for quantification of myocardial contrast enhancement. This approach was tested in 13 anesthetized pigs during continuous intravenous infusion of contrast at baseline, left anterior descending coronary artery occlusion, and reperfusion. Regional pixel intensity was calculated for each consecutive end-systolic frame after a high-energy ultrasound impulse, and fitted with an exponential function. Perfusion defects caused by occlusion of left anterior descending coronary artery were confirmed by a significant decrease in both postimpulse steady-state intensity and the initial rate of contrast replenishment (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.05), which were reversed with reperfusion. Automated measurements of myocardial intensity correlated highly with conventional manual tracing (r = 0.90 to 0.97), and resulted in improved signal-to-noise ratios. This technique allows translation-free quantification of regional myocardial perfusion, without the need for manual tracing.
Background: Exercise-induced changes in arterial function could contribute to a hypertensive resp... more Background: Exercise-induced changes in arterial function could contribute to a hypertensive response to exercise (HRE) in older individuals. We performed the present analysis to define the acute arterial stiffness response to exercise in ambulatory older adults. Methods: Thirty-nine Veterans (&gt;60 years old), without known cardiovascular disease, participated in this study, including 19 Veterans who were hypertensive (70.8 ± 6.8 years, 53% women) and 20 Veterans who were normotensive (72.0 ± 9.3 years, 40% women). Arterial stiffness parameters were measured locally with carotid artery ultrasound and regionally with carotid–femoral pulse wave velocity (cfPWV) before and during the 10 min after participants performed a Balke maximal exercise treadmill stress test. Results: The arterial stiffness response to exercise was similar for control and hypertensive participants. At 6 min postexercise, cfPWV was significantly increased (Δ1.5 ± 1.9 m/s, P = 0.004) despite mean blood pressure (BP) having returned to its baseline value (Δ1 ± 8 mmHg, P = 0.79). Arterial mechanics modeling also showed BP-independent increases in arterial stiffness with exercise (P &lt; 0.05). Postexercise cfPWV was correlated with postexercise SBP (r = 0.50, P = 0.004) while baseline cfPWV (r = 0.13, P = 1.00), and postexercise total peripheral resistance (r = −0.18, P = 1.00) were not. Conclusion: In older Veterans, exercise increases arterial stiffness independently of BP and the arterial stiffness increase with exercise is associated with increased postexercise SBP. BP-independent increases in arterial stiffness with exercise could contribute to a HRE in older adults.
We tested the feasibility of improved evaluation of left ventricular (LV) wall motion using still... more We tested the feasibility of improved evaluation of left ventricular (LV) wall motion using still-frame-parametric images of local video intensity oscillations. In 8 anesthetized pigs, baseline parametric images showed bright hands in the area spanned by endocardial motion, which gradually decreased in brightness and thickness in the territory of the occluded coronary artery. In 30 patients with contrast-enhanced echocardiograms, "gold standard" for wall motion was determined from independent interpretations of dynamic images made by three experienced reviewers. Dynamic images were independently classified by 3 inexperienced and 3 intermediate experience level readers. Interpretation was then repeated in combination with parametric images. Compared with the "gold standard", evaluation of wall motion correlated with the readers' experience and was significantly improved by adding parametric images
Introduction: Vasodilation can paradoxically increase arterial stiffness in older, hypertensive a... more Introduction: Vasodilation can paradoxically increase arterial stiffness in older, hypertensive adults. This study modeled increasing smooth muscle tone as a therapeutic strategy to improve central arterial dysfunction in hypertension using participant-specific simulations. Methods: Participant-specific models of the carotid artery were parameterized from vascular ultrasound measures of nitroglycerin-induced vasodilation in 18 hypertensive veterans. The acute changes in carotid artery mechanics were simulated for changes of ±2, ±4, and ±6% in smooth muscle tone and ±5, ±10, and ±15 mmHg in mean arterial pressure (MAP). The chronic carotid artery adaptations were simulated based on the hypothesis that the carotid artery will remodel wall-cross sectional area to maintain mechanical homeostasis. Results: A 6% increase in smooth muscle tone acutely decreased carotid pulse wave velocity from 6.89 ± 1.24 m/s to 5.83 ± 1.73 m/s, and a 15 mmHg decrease in MAP decreased carotid pulse wave velocity to 6.17 ± 1.23 m/s. A 6% increase in smooth muscle tone acutely decreased wall stress from 76.2 ± 12.3 to 64.2 ± 10.4 kPa, and a 15 mmHg decrease in MAP decreased wall stress to 60.6 ± 10.7 kPa. A 6% increase in smooth muscle tone chronically decreased wall cross-sectional area from 18.3 ± 5.4 to 15.2 ± 4.9 mm2, and a 15 mmHg decrease in MAP decreased wall cross-sectional area to 14.3 ± 4.6 mm2. Conclusion: In participant-specific simulation, increasing smooth muscle tone can have a stronger or equivalent effect on carotid artery mechanics compared with decreasing blood pressure. Increasing central arterial smooth muscle tone may be a novel therapeutic target to improve central arterial dysfunction in older, hypertensive adults and should be a focus of future research.
Background: Elastic arteries stiffen via 2 main mechanisms: (1) load-dependent stiffening from hi... more Background: Elastic arteries stiffen via 2 main mechanisms: (1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to changes in the vessel wall. It is unknown how these different mechanisms contribute to incident cardiovascular disease (CVD) events. Methods: The MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study of 6814 men and women without CVD at enrollment, from 6 communities in the United States. MESA participants with B-mode carotid ultrasound and brachial blood pressure at baseline Exam in (2000–2002) and CVD surveillance (mean follow-up 14.3 years through 2018) were included (n=5873). Peterson’s elastic modulus was calculated to represent total arterial stiffness. Structural stiffness was calculated by adjusting Peterson’s elastic modulus to a standard blood pressure of 120/80 mm Hg with participant-specific models. Load-dependent stiffness was the difference between total and structural stiffness. Results: In Cox models adjusted for traditional risk factors, load-dependent stiffness was significantly associated with higher incidence of CVD events (hazard ratio/100 mm Hg, 1.21 [95% CI, 1.09–1.34] P &lt;0.001) events while higher structural stiffness was not (hazard ratio, 1.03 [95% CI, 0.99–1.07] P =0.10). Analysis of participants who were normotensive (blood pressure &lt;130/80, no antihypertensives) at baseline exam (n=2122) found higher load-dependent stiffness was also associated with significantly higher incidence of hypertension (hazard ratio, 1.53 [95% CI, 1.35–1.75] P &lt;0.001) while higher structural stiffness was not (hazard ratio, 1.03 [95% CI, 0.99–1.07] P =0.16). Conclusions: These results provide valuable new insights into mechanisms underlying the association between arterial stiffness and CVD. Load-dependent stiffness was significantly associated with CVD events but structural stiffness was not.
Journal of The American Society of Echocardiography, Feb 1, 2002
There is no method to objectively evaluate left ventricular (LV) function from contrast-enhanced ... more There is no method to objectively evaluate left ventricular (LV) function from contrast-enhanced images. We tested the feasibility of evaluating regional LV function by using power modulation imaging. In protocol 1, 9 anesthetized closed-chest pigs were studied. Images were obtained during contrast infusion at baseline, during LAD occlusion and reperfusion. In protocol 2, images were obtained in 20 patients (14 wall-motion abnormalities; 6 controls) during contrast enhancement. Off-line, frame-by-frame, semiautomated endocardial border detection was followed by color encoding of endocardial motion, followed by segmentation and calculation of regional fractional area changes. In all animals, coronary occlusions resulted in hypokinesis and decreased fractional area changes in LAD-related segments only, which were reversed during reperfusion. In patients, wall-motion analysis was in agreement with an expert reader of dynamic images in 92.5% segments, with interobserver variability of 12.5%. Color encoding of endocardial motion from contrast-enhanced power modulation images allows accurate quantitative assessment of regional LV function.
Background and PurposeMany health effects of sleep apnea (SA) may be mediated through accelerated... more Background and PurposeMany health effects of sleep apnea (SA) may be mediated through accelerated atherosclerosis. We examined the associations of snoring and several measurements of SA with subclinical carotid atherosclerosis in a large multiethnic population sample.MethodsThis analysis included 1615 participants (mean age 68 years) from examination 5 (2010-2013) of the Multi-Ethnic Study of Atherosclerosis. Sleep measures including SA (apnea-hypopnea index [AHI 4%] ≥15 events/hour) were derived from full in-home polysomnography. Carotid atherosclerosis was measured using high-resolution B-mode ultrasound. Multivariable linear and logistic regression models were used to evaluate the associations between sleep exposures with carotid intima-media thickness (CIMT) and the presence of carotid plaque, respectively. Effect modification by age, sex, and race/ethnicity was examined.ResultsIn multivariable analysis, SA was associated with an increased odds of carotid plaque presence in individuals aged <68 years (odds ratio [OR], 1.47; 95% confidence interval [CI] 1.05 to 2.06) but not in older individuals (OR 0.95; 95% CI 0.67 to 1.37, p-interaction=0.078). Greater hypoxemia (sleep time <90% saturation) was associated with increasing CIMT in younger (0.028 ± 0.014 mm) but not in older individuals (−0.001 ± 0.013 mm, p-interaction= 0.106). Self-reported snoring was not associated with carotid atherosclerosis. In assessing race-specific outcomes, greater hypoxemia was associated with increased CIMT in Blacks (0.049 ±0.017 mm, p-interaction=0.033).ConclusionsIn this large multiethnic population-based sample, sleep disturbances are associated with subclinical carotid atherosclerosis in both men and women, particularly in those <68 years. The mechanisms underlying the association between sleep apnea and carotid atherosclerosis may differ for carotid plaque and CIMT.
Background Color kinesis is a new technology for the echocardiographic assessment of left ventric... more 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.
Objectives: In pulmonary hypertension associated with HFpEF (PH-HFpEF), identifying mechanisms of... more Objectives: In pulmonary hypertension associated with HFpEF (PH-HFpEF), identifying mechanisms of right ventricular: pulmonary arterial (RV:PA) uncoupling can be leveraged for sub-phenotyping and targeted therapies. In this study, we aim to distinguish mechanisms of RV:PA uncoupling in PH-HFpEF due to high RV afterload (afterload-sensitive; AS) and impaired left ventricular-interventricular septal contributions to RV function (ventricular interdependence; VI). Methods: Subjects (n=13) with early-stage PH (per echo) and NYHA II-III dyspnea were prospectively enrolled. Exclusion criteria: advanced disease with NYHA IV, LVEF &lt;50%. All subjects underwent rest-to-exercise (every 25 watts) invasive cardiopulmonary exercise test and echo (for impedance: characteristic for pulsatile load Z C , input for steady load Z 0 ), followed by RV real-time pressure volume (PV)-loops. Subsequently, a cardiac MRI was performed with temporal resolution of 25-30 msec. Five study subjects had isolated post-capillary (Ipc-PH), 5 had pulmonary arterial hypertension, 2 had combined pre/post-capillary PH, and 1 had no PH. Results: With exercise, impedance (Z C and Z 0 ) increased or remained unchanged in all PH subjects but decreased in the subject with no PH. Z C (time domain method) was correlated with PV-loop based uncoupling (end-systolic to elastance ratio Ees:Ea) among Ipc-PH subjects (r 2 =0.40, p&lt;0.01), but had poor correlation in other phenotypes (r2=0.01, p=0.11). As next step, within each IpcPH subject, correlation of Z C with Ees:Ea (with repeated measures across exercise stages) was determined to identify afterload sensitivity (Figure). Cardiac MRI-based regional strain was used to identify ventricular interdependence; defined as reduced strain of interventricular septum (Figure). Conclusions: Multimodality methods to assess RV:PA uncoupling in PH-HFpEF can identify afterload-sensitive phenotypes, which may benefit from focused interventions.
Background: The acute cardiovascular effects of electronic nicotine delivery devices (ENDs) have ... more Background: The acute cardiovascular effects of electronic nicotine delivery devices (ENDs) have not been well-characterized. We hypothesized differences in acute cardiovascular and autonomic function responses to use of ENDS by chronic ENDs users (“vapers”), use of combustible cigarettes by chronic “smokers,” and no product use among non-smoking/non-vaping controls. Methods: CLUES (HL1393301) was a cross-sectional study of 395 individuals: 164 exclusive vapers (exhaled carbon monoxide [CO] &lt;5 ppm, positive urine NicCheck I test), 117 exclusive smokers (CO &gt;5 ppm, positive urine NicCheck), and 114 non-vaping/non-smoking controls (CO &lt;5 ppm, negative urine NicCheck). We measured systolic and diastolic blood pressure (BP), heart rate (HR), brachial artery diameter, and time domain HR variability (root mean square differences in successive normal intervals [RMSSD]; % adjacent normal intervals &gt;50 ms [PNN50]) before and 15’ after a product use challenge. Linear mixed models were created to predict outcome measures from group, time, and group*time with age, sex, and race as covariates, followed by group contrasts via post-hoc t-tests with Bonferroni-corrected p values. Results: Vapers were a mean (SD) 27.4 (10.6) years old (39% female, 86% white) and had vaped for 4.1 (2.7) years. Smokers were 42.8 (13.8) years old (44% female, 56% white) and had smoked for 23.0 (13.0) years. Controls were 30.8 (11.9) years old (50% female, 69% white). Model-adjusted mean (95% CIs) outcomes and p values for between group differences in challenge responses are in the Figure. Compared to controls, vapers had greater increases in systolic BP, diastolic BP, and HR (all p &lt; 0.002) and greater reductions in brachial artery diameter, RMSSD, and PNN50 (all p &lt; 0.003) than controls, with values similar to smokers. Conclusion: Chronic vapers showed acute increases in BP and HR, vasoconstriction, and reductions in time domain HR variability after using ENDS, similar to cigarette use by smokers.
Introduction: Stiff arteries increase the risk of end organ damage to the brain and kidneys. Arte... more Introduction: Stiff arteries increase the risk of end organ damage to the brain and kidneys. Arterial stiffness can be separated into two main mechanisms: 1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to remodeling of the vessel wall. The relationship between arterial stiffness mechanisms and end organ damage risk is unknown. Hypothesis: Both stiffness mechanisms will be significantly associated with chronic kidney disease (CKD), dementia, and mortality. Methods: MESA participants with B-mode carotid ultrasound in 2000-2002 were included in this study (n=6147). Carotid pulse wave velocity (cPWV) was calculated to represent total stiffness. Structural stiffness was calculated by adjusting cPWV to a 120/80 BP with participant-specific models. Load dependent (LD) stiffness was the difference of total and structural stiffness. Associations with incident CKD, dementia defined by ICD codes, and mortality were assessed with Cox models adjusted for age, sex, race/ethnicity, education, study site, smoking, pack-years, diabetes, BMI, SBP, non-HDL-C, BP medication, and lipid medication. Results: During 14.3±4.8 years of follow-up, 773 CKD events, 535 dementia events, and 1529 deaths occurred. Total cPWV was associated with mortality (HR 1.04 [1.01-1.08], p=0.02) and dementia (HR 1.06 [1.01 - 1.12], p=0.03). Structural cPWV was significantly associated with mortality (HR 1.04 [1.00 - 1.08], p=0.04) but not CKD (HR 1.00 [0.94-1.05], p=0.86) or dementia (HR 1.06 [0.99-1.13], p=0.06). LD cPWV was associated with CKD (HR 1.38 [1.17 - 1.63], p&lt;0.001) but not mortality (HR 1.11 [0.99-1.25], p=0.07) or dementia (HR 1.14 [0.94-1.38], p=0.19). Conclusions: Structural carotid artery stiffness was significantly associated with all-cause mortality, while LD stiffness was significantly associated with CKD. Total carotid stiffness was associated with incident dementia but LD and structural stiffness mechanisms were not.
Journal of the American Heart Association, Apr 4, 2023
Background Arterial stiffness can be separated into 2 main mechanisms: (1) load‐dependent stiffen... more Background Arterial stiffness can be separated into 2 main mechanisms: (1) load‐dependent stiffening from higher blood pressure and (2) structural stiffening due to remodeling of the vessel wall. The relationship between stiffness mechanisms and end organ damage is unknown. Methods and Results MESA (Multi‐Ethnic Study of Atherosclerosis) participants with carotid ultrasound were included in this study (n=6147). Carotid pulse wave velocity (cPWV) was calculated to represent total stiffness. Structural stiffness was calculated by adjusting cPWV to a 120/80 mm Hg blood pressure with participant‐specific models. Load‐dependent stiffness was the difference of total and structural stiffness. Associations with incident chronic kidney disease (CKD), dementia, and mortality were assessed with adjusted Cox models. During 14.3±4.8 years of follow‐up, 773 CKD events, 535 dementia events, and 1529 deaths occurred. Total cPWV was associated with mortality (hazard ratio [HR], per 1 m/s, 1.04 [95% CI, 1.01–1.08], P =0.02) and dementia (HR, 1.06 [95% CI, 1.01–1.12], P =0.03) but not CKD (HR, 1.03 [95% CI, 0.98–1.08], P =0.33). Structural cPWV was significantly associated with mortality (HR, 1.04 [95% CI, 1.00–1.08], P =0.04) but not CKD (HR, 1.00 [95% CI, 0.94–1.05], P =0.86) or dementia (HR, 1.06 [95% CI, 0.99–1.13], P =0.06). Load‐dependent cPWV was significantly associated with CKD (HR, 1.38 [95% CI, 1.17–1.63], P &lt;0.001) but not mortality (HR, 1.11 [95% CI, 0.99–1.25], P =0.07) or dementia (HR, 1.14 [95% CI, 0.94–1.38], P =0.19). Conclusions The mechanisms of arterial stiffness were associated with all‐cause mortality and CKD. Structural stiffness was associated with all‐cause mortality, and load‐dependent stiffness was associated with CKD. Total stiffness was associated with dementia but load‐dependent and structural stiffness were not.
Journal of The American Society of Echocardiography, Feb 1, 2003
Quantitative analysis of myocardial perfusion is currently based on manual tracing and frame-by-f... more Quantitative analysis of myocardial perfusion is currently based on manual tracing and frame-by-frame realignment of regions of interest. We developed a technique for semiautomated identification of myocardial regions from power modulation images as a potential tool for quantification of myocardial contrast enhancement. This approach was tested in 13 anesthetized pigs during continuous intravenous infusion of contrast at baseline, left anterior descending coronary artery occlusion, and reperfusion. Regional pixel intensity was calculated for each consecutive end-systolic frame after a high-energy ultrasound impulse, and fitted with an exponential function. Perfusion defects caused by occlusion of left anterior descending coronary artery were confirmed by a significant decrease in both postimpulse steady-state intensity and the initial rate of contrast replenishment (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;.05), which were reversed with reperfusion. Automated measurements of myocardial intensity correlated highly with conventional manual tracing (r = 0.90 to 0.97), and resulted in improved signal-to-noise ratios. This technique allows translation-free quantification of regional myocardial perfusion, without the need for manual tracing.
Background: Exercise-induced changes in arterial function could contribute to a hypertensive resp... more Background: Exercise-induced changes in arterial function could contribute to a hypertensive response to exercise (HRE) in older individuals. We performed the present analysis to define the acute arterial stiffness response to exercise in ambulatory older adults. Methods: Thirty-nine Veterans (&gt;60 years old), without known cardiovascular disease, participated in this study, including 19 Veterans who were hypertensive (70.8 ± 6.8 years, 53% women) and 20 Veterans who were normotensive (72.0 ± 9.3 years, 40% women). Arterial stiffness parameters were measured locally with carotid artery ultrasound and regionally with carotid–femoral pulse wave velocity (cfPWV) before and during the 10 min after participants performed a Balke maximal exercise treadmill stress test. Results: The arterial stiffness response to exercise was similar for control and hypertensive participants. At 6 min postexercise, cfPWV was significantly increased (Δ1.5 ± 1.9 m/s, P = 0.004) despite mean blood pressure (BP) having returned to its baseline value (Δ1 ± 8 mmHg, P = 0.79). Arterial mechanics modeling also showed BP-independent increases in arterial stiffness with exercise (P &lt; 0.05). Postexercise cfPWV was correlated with postexercise SBP (r = 0.50, P = 0.004) while baseline cfPWV (r = 0.13, P = 1.00), and postexercise total peripheral resistance (r = −0.18, P = 1.00) were not. Conclusion: In older Veterans, exercise increases arterial stiffness independently of BP and the arterial stiffness increase with exercise is associated with increased postexercise SBP. BP-independent increases in arterial stiffness with exercise could contribute to a HRE in older adults.
We tested the feasibility of improved evaluation of left ventricular (LV) wall motion using still... more We tested the feasibility of improved evaluation of left ventricular (LV) wall motion using still-frame-parametric images of local video intensity oscillations. In 8 anesthetized pigs, baseline parametric images showed bright hands in the area spanned by endocardial motion, which gradually decreased in brightness and thickness in the territory of the occluded coronary artery. In 30 patients with contrast-enhanced echocardiograms, "gold standard" for wall motion was determined from independent interpretations of dynamic images made by three experienced reviewers. Dynamic images were independently classified by 3 inexperienced and 3 intermediate experience level readers. Interpretation was then repeated in combination with parametric images. Compared with the "gold standard", evaluation of wall motion correlated with the readers' experience and was significantly improved by adding parametric images
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