Multiaxial pressure-strain analysis of regional myocardial work in the setting of graded coronary stenoses and dobutamine stress.

We present a detailed analysis of regional myocardial blood flow and work to better understand the effects of coronary stenoses and low-dose dobutamine stress. Our analysis is based on a unique open-chest model in anesthetized canines that features invasive hemodynamic monitoring, microsphere-based blood flow analysis, and an extensive three-dimensional (3-D) sonomicrometer array that provides multiaxial deformational assessments in the ischemic, border, and remote vascular territories. We use this model to construct regional pressure-strain loops for each territory and quantify the loop subcomponent areas that reflect myocardial work contributing to the ejection of blood and wasted work that does not. We demonstrate that reductions in coronary blood flow markedly alter the shapes and temporal relationships of pressure-strain loops, as well as the magnitudes of their total and subcomponent areas. Specifically, we show that moderate stenoses in the mid-left anterior descending coronary artery decrease regional midventricle myocardial work indices and substantially increase indices of wasted work. In the midventricle, these effects are most pronounced along the radial and longitudinal axes, with more modest effects along the circumferential axis. We further demonstrate that low-dose dobutamine can help to restore or even improve function, but often at the cost of increased wasted work. This detailed, multiaxial analysis provides unique insight into the physiology and mechanics of the heart in the presence of ischemia and low-dose dobutamine, with potential implications in many areas, including the detection and characterization of ischemic heart disease and the use of inotropic support for low cardiac output.NEW & NOTEWORTHY Our unique experimental model assesses cardiac pressure-strain relationships along multiple axes in multiple regions. We demonstrate that moderate coronary stenoses decrease regional myocardial work and increase wasted work and that low-dose dobutamine can help to restore myocardial function, but often with further increases in wasted work. Our findings highlight the significant directional variation of cardiac mechanics and demonstrate potential advantages of pressure-strain analyses over traditional, purely deformational measures, especially in characterizing physiological changes related to dobutamine.

Regional myocardial strain analysis via 2D speckle tracking echocardiography: validation with sonomicrometry and correlation with regional blood flow in the presence of graded coronary stenoses and dobutamine stress.

BACKGROUND: Quantitative regional strain analysis by speckle tracking echocardiography (STE) may be particularly useful in the assessment of myocardial ischemia and viability, although reliable measurement of regional strain remains challenging, especially in the circumferential and radial directions. We present an acute canine model that integrates a complex sonomicrometer array with microsphere blood flow measurements to evaluate regional myocardial strain and flow in the setting of graded coronary stenoses and dobutamine stress. We apply this unique model to rigorously evaluate a commercial 2D STE software package and explore fundamental regional myocardial flow-function relationships. METHODS: Sonomicrometers (16 crystals) were implanted in epicardial and endocardial pairs across the anterior myocardium of anesthetized open chest dogs (n = 7) to form three adjacent cubes representing the ischemic, border, and remote regions, as defined by their relative locations to a hydraulic occluder on the mid-left anterior descending coronary artery (LAD). Additional cardiac (n = 3) and extra-cardiac (n = 3) reference crystals were placed to define the cardiac axes and aid image registration. 2D short axis echocardiograms, sonometric data, and microsphere blood flow data were acquired at baseline and in the presence of mild and moderate LAD stenoses, both before and during low-dose dobutamine stress (5 µg/kg/min). Regional end-systolic 2D STE radial and circumferential strains were calculated with commercial software (EchoInsight) and compared to those determined by sonomicrometry and to microsphere blood flow measurements. Post-systolic indices (PSIs) were also calculated for radial and circumferential strains. RESULTS: Low-dose dobutamine augmented both strain and flow in the presence of mild and moderate stenoses. Regional 2D STE strains correlated moderately with strains assessed by sonomicrometry (Rradial = 0.56, p < 0.0001; Rcirc = 0.55, p < 0.0001) and with regional flow quantities (Rradial = 0.61, Rcirc = 0.63). Overall, correspondence between 2D STE and sonomicrometry was better in the circumferential direction (Bias ± 1.96 SD: - 1.0 ± 8.2% strain, p = 0.06) than the radial direction (5.7 ± 18.3%, p < 0.0001). Mean PSI values were greatest in low flow conditions and normalized with low-dose dobutamine. CONCLUSIONS: 2D STE identifies changes in regional end-systolic circumferential and radial strain produced by mild and moderate coronary stenoses and low-dose dobutamine stress. Regional 2D STE end-systolic strain measurements correlate modestly with regional sonomicrometer strain and microsphere flow measurements.

Flow network tracking for spatiotemporal and periodic point matching: Applied to cardiac motion analysis.

The accurate quantification of left ventricular (LV) deformation/strain shows significant promise for quantitatively assessing cardiac function for use in diagnosis and therapy planning. However, accurate estimation of the displacement of myocardial tissue and hence LV strain has been challenging due to a variety of issues, including those related to deriving tracking tokens from images and following tissue locations over the entire cardiac cycle. In this work, we propose a point matching scheme where correspondences are modeled as flow through a graphical network. Myocardial surface points are set up as nodes in the network and edges define neighborhood relationships temporally. The novelty lies in the constraints that are imposed on the matching scheme, which render the correspondences one-to-one through the entire cardiac cycle, and not just two consecutive frames. The constraints also encourage motion to be cyclic, which an important characteristic of LV motion. We validate our method by applying it to the estimation of quantitative LV displacement and strain estimation using 8 synthetic and 8 open-chested canine 4D echocardiographic image sequences, the latter with sonomicrometric crystals implanted on the LV wall. We were able to achieve excellent tracking accuracy on the synthetic dataset and observed a good correlation with crystal-based strains on the in-vivo data.

Molecular Imaging of the Heart.

Multimodality cardiovascular imaging is routinely used to assess cardiac function, structure, and physiological parameters to facilitate the diagnosis, characterization, and phenotyping of numerous cardiovascular diseases (CVD), as well as allows for risk stratification and guidance in medical therapy decision-making. Although useful, these imaging strategies are unable to assess the underlying cellular and molecular processes that modulate pathophysiological changes. Over the last decade, there have been great advancements in imaging instrumentation and technology that have been paralleled by breakthroughs in probe development and image analysis. These advancements have been merged with discoveries in cellular/molecular cardiovascular biology to burgeon the field of cardiovascular molecular imaging. Cardiovascular molecular imaging aims to noninvasively detect and characterize underlying disease processes to facilitate early diagnosis, improve prognostication, and guide targeted therapy across the continuum of CVD. The most-widely used approaches for preclinical and clinical molecular imaging include radiotracers that allow for high-sensitivity in vivo detection and quantification of molecular processes with single photon emission computed tomography and positron emission tomography. This review will describe multimodality molecular imaging instrumentation along with established and novel molecular imaging targets and probes. We will highlight how molecular imaging has provided valuable insights in determining the underlying fundamental biology of a wide variety of CVDs, including: myocardial infarction, cardiac arrhythmias, and nonischemic and ischemic heart failure with reduced and preserved ejection fraction. In addition, the potential of molecular imaging to assist in the characterization and risk stratification of systemic diseases, such as amyloidosis and sarcoidosis will be discussed. © 2019 American Physiological Society. Compr Physiol 9:477-533, 2019.

Prevalence of Metabolic Syndrome in Patients with HIV in the Era of Highly Active Antiretroviral Therapy.

OBJECTIVES: Since the introduction of combination antiretroviral therapy (cART) as the standard of care for HIV disease, there has been a precipitous decline in the death rate due to HIV/ AIDS. The purpose of this study was to report the prevalence of metabolic syndrome in HIV infected patients. METHODS: Retrospective, cross-sectional, observational study of 259 patients with HIV infection treated with cART from an urban community hospital. Metabolic syndrome prevalence was defined using the International Diabetes Federation (IDF) and the U.S. National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria. Study patients were included regardless of the duration of cART. RESULTS: The prevalence of metabolic syndrome was 27% using IDF criteria and 26% using ATP III criteria. Logistic regression analysis found an association between treatment with the protease inhibitor darunavir and metabolic syndrome. (OR 3.32 with 95% confidence interval between 1.54 and 7.15). CONCLUSION: There is a high prevalence of metabolic syndrome and obesity in HIV patients treated with cART, especially those taking the protease inhibitor darunavir.