Personalized echocardiography: clinical applications of advanced echocardiography and future directions.

Future cardiology practice will be increasingly individualized, and thus to maintain its central role, echocardiography must keep pushing to expand the boundaries of real-time data acquisition from tissue and fluid motion, and yet still provide efficient and timely data analysis that leads to succinct, clear clinical recommendations tailored to each person in our care. In this article, recent efforts to expand echocardiography techniques into an era of increasingly personalized cardiology, including advances in color-coded tissue Doppler, 3D echocardiography and complex exercise stress echocardiography are described. The common metric for success in each of these efforts is the development of robust and institutionally supportable echocardiography protocols for specific cardiology disease populations that currently may be underdiagnosed and/or undertreated. The common result in each case should be the creation of new guidelines that can supplement the current standard protocols advocated by professional echocardiography organizations.

Customized exercise echocardiography: beyond detection of coronary artery disease.

Exercise echocardiography has been established as a reliable diagnostic tool for assessment of myocardial ischemia. However, more recent advances in its technique have expanded its routine clinical use to include quantification of exercise-induced diastolic dysfunction, exercise-induced pulmonary hypertension, and dynamic assessment of mitral and aortic valve function. The indications for exercise echocardiography have increased to include cardiac symptoms such as exertional dyspnea, fatigue, and limited exercise capacity. In light of its expanded capability for evaluating cardiovascular function, we believe that exercise echocardiography should be utilized in a new paradigm of personalized cardiology, in which we regularly investigate individual patient symptoms for endpoints beyond critical myocardial ischemia, for example, exercise-induced pulmonary hypertension. We refer to this refocused use of exercise echocardiography as "customized exercise echocardiography." In this review article, we present current scientific evidence to support our proposed role and discuss the logistical requirements for proper test performance of customized exercise echocardiography.

Proinflammatory phenotype of perivascular adipocytes: influence of high-fat feeding.

Adipose tissue depots originate from distinct precursor cells, are functionally diverse, and modulate disease processes in a depot-specific manner. However, the functional properties of perivascular adipocytes, and their influence on disease of the blood vessel wall, remain to be determined. We show that human coronary perivascular adipocytes exhibit a reduced state of adipocytic differentiation as compared with adipocytes derived from subcutaneous and visceral (perirenal) adipose depots. Secretion of antiinflammatory adiponectin is markedly reduced, whereas that of proinflammatory cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1, is markedly increased in perivascular adipocytes. These depot-specific differences in adipocyte function are demonstrable in both freshly isolated adipose tissues and in vitro-differentiated adipocytes. Murine aortic arch perivascular adipose tissues likewise express lower levels of adipocyte-associated genes as compared with subcutaneous and visceral adipose tissues. Moreover, 2 weeks of high-fat feeding caused further reductions in adipocyte-associated gene expression, while upregulating proinflammatory gene expression, in perivascular adipose tissues. These changes were observed in the absence of macrophage recruitment to the perivascular adipose depot. We conclude that perivascular adipocytes exhibit reduced differentiation and a heightened proinflammatory state, properties that are intrinsic to the adipocytes residing in this depot. Dysfunction of perivascular adipose tissue induced by fat feeding suggests that this unique adipose depot is capable of linking metabolic signals to inflammation in the blood vessel wall.

Regulation of endotoxin-induced proinflammatory activation in human coronary artery cells: expression of functional membrane-bound CD14 by human coronary artery smooth muscle cells.

Low-level endotoxemia has been identified as a powerful risk factor for atherosclerosis. However, little is known about the mechanisms that regulate endotoxin responsiveness in vascular cells. We conducted experiments to compare the relative responses of human coronary artery endothelial cells (HCAEC) and smooth muscle cells (HCASMC) to very low levels of endotoxin, and to elucidate the mechanisms that regulate endotoxin responsiveness in vascular cells. Endotoxin (10-fold higher in magnitude at >10-fold lower threshold concentrations (10-30 pg/ml) compared with HCAEC. This remarkable sensitivity of HCASMC to very low endotoxin concentrations, comparable to that found in circulating monocytes, was not due to differential expression of TLR4, which was detected in HCAEC, HCASMC, and intact coronary arteries. Surprisingly, membrane-bound CD14 was detected in seven different lines of HCASMC, conferring responsiveness to endotoxin and to lipoteichoic acid, a product of Gram-positive bacteria, in these cells. These results suggest that the low levels of endotoxin associated with increased risk for atherosclerosis are sufficient to produce inflammatory responses in coronary artery cells. Because CD14 recognizes a diverse array of inflammatory mediators and functions as a pattern recognition molecule in inflammatory cells, expression of membrane-bound CD14 in HCASMC implies a potentially broader role for these cells in transducing innate immune responses in the vasculature.