Background Although the Thrombolysis in Myocardial Infarction (TIMI) flow grade is a valuable and widely used qualitative measure in angiographic trials, it is limited by its subjective and categorical nature. Methods and Results In normal patients and patients with acute myocardial infarction (MI) (TIMI 4), the number of cineframes needed for dye to reach standardized distal landmarks was counted to objectively assess an index of coronary blood flow as a continuous variable. The TIMI frame-counting method was reproducible (mean absolute difference between two injections, 4.7±3.9 frames, n=85). In 78 consecutive normal arteries, the left anterior descending coronary artery (LAD) TIMI frame count (36.2±2.6 frames) was 1.7 times longer than the mean of the right coronary artery (20.4±3.0) and circumflex counts (22.2±4.1, P<.001 for either versus LAD). Therefore, the longer LAD frame counts were corrected by dividing by 1.7 to derive the corrected TIMI frame count (CTFC). The mean CTFC in culprit arteries 90...

TIMI Frame Count A Quantitative Method of Assessing Coronary Artery Flow

BACKGROUND Precise knowledge of the expected "normal" lumen diameter at a given coronary anatomic location is a first step toward developing a quantitative estimate of coronary disease severity that could be more useful than the traditional "percent stenosis." METHODS AND RESULTS Eighty-three arteriograms were carefully selected from among 9,160 consecutive studies for their smooth lumen borders indicating freedom from atherosclerotic disease. Of these, 60 men and 10 women had no abnormalities of cardiac function, seven men had idiopathic dilated cardiomyopathy, and six men had left ventricular hypertrophy associated with significant aortic stenosis. Lumen diameter was measured at 96 points in 32 defined coronary segments or major branches. Measurements were scaled to the catheter, corrected for imaging distortion, and had a mean repeat measurement error of 0.12 mm. When sex, anatomic dominance, and branch length were accounted for, normal lumen diameter at each of the standard anatomic points could usually be specified with a population variance of +/- 0.6 mm or less (SD) and coefficient of variation of less than 0.25 (SD/mean). For example, the left main artery measured 4.5 +/- 0.5 mm, the proximal left anterior descending coronary artery (LAD) 3.7 +/- 0.4 mm, and the distal LAD 1.9 +/- 0.4 mm. For the LAD, lumen diameter was not affected by anatomic dominance (right versus left), but for the right coronary artery, proximal diameter varied between 3.9 +/- 0.6 and 2.8 +/- 0.5 mm (p less than 0.01) and for the left circumflex, between 3.4 +/- 0.5 and 4.2 +/- 0.6 mm (p less than 0.01). Women had smaller epicardial arterial diameter than men (-9%; p less than 0.001), even after normalization for body surface area (p less than 0.01). Branch artery caliber was unaffected by the anatomic dominance but increased with branch length, expressed as a fraction of the origin-to-apex distance (p less than 0.001). Lumen diameter was not affected by age or by vessel tortuosity but was significantly increased among men with left ventricular hypertrophy (+ 17%; p less than 0.001) or dilated cardiomyopathy (+ 12%; p less than 0.001). CONCLUSIONS This is a reference normal data set against which to compare lumen dimensions in various pathological states. It should be of particular value in the investigation of diffuse atherosclerotic disease.

Lumen diameter of normal human coronary arteries. Influence of age, sex, anatomic variation, and left ventricular hypertrophy or dilation.

Methods and apparatus are provided for renal neuromodulation using a pulsed electric field to effectuate electroporation or electrofusion. It is expected that renal neuromodulation (e.g., denervation) may, among other things, reduce expansion of an acute myocardial infarction, reduce or prevent the onset of morphological changes that are affiliated with congestive heart failure, and/or be efficacious in the treatment of end stage renal disease. Embodiments of the present invention are configured for percutaneous intravascular delivery of pulsed electric fields to achieve such neuromodulation.

Methods and apparatus for renal neuromodulation

A distributed model of the human arterial tree including all main systemic arteries coupled to a heart model is developed. The one-dimensional (1-D) form of the momentum and continuity equations is solved numerically to obtain pressures and flows throughout the systemic arterial tree. Intimal shear is modeled using the Witzig-Womersley theory. A nonlinear viscoelastic constitutive law for the arterial wall is considered. The left ventricle is modeled using the varying elastance model. Distal vessels are terminated with three-element windkessels. Coronaries are modeled assuming a systolic flow impediment proportional to ventricular varying elastance. Arterial dimensions were taken from previous 1-D models and were extended to include a detailed description of cerebral vasculature. Elastic properties were taken from the literature. To validate model predictions, noninvasive measurements of pressure and flow were performed in young volunteers. Flow in large arteries was measured with MRI, cerebral flow with ultrasound Doppler, and pressure with tonometry. The resulting 1-D model is the most complete, because it encompasses all major segments of the arterial tree, accounts for ventricular-vascular interaction, and includes an improved description of shear stress and wall viscoelasticity. Model predictions at different arterial locations compared well with measured flow and pressure waves at the same anatomical points, reflecting the agreement in the general characteristics of the "generic 1-D model" and the "average subject" of our volunteer population. The study constitutes a first validation of the complete 1-D model using human pressure and flow data and supports the applicability of the 1-D model in the human circulation.

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Validation of a one-dimensional model of the systemic arterial tree.

Methods and apparatus are provided for thermally-induced renal neuromodulation. Thermally-induced renal neuromodulation may be achieved via direct and/or via indirect application of thermal energy to heat or cool neural fibers that contribute to renal function, or of vascular structures that feed or perfuse the neural fibers. In some embodiments, parameters of the neural fibers, of non-target tissue, or of the thermal energy delivery element, may be monitored via one or more sensors for controlling the thermally-induced neuromodulation. In some embodiments, protective elements may be provided to reduce a degree of thermal damage induced in the non-target tissues. In some embodiments, thermally-induced renal neuromodulation is achieved via delivery of a pulsed thermal therapy.

Methods and apparatus for thermally-induced renal neuromodulation

The clinically important coronary segmental anatomy has been described in a format useful for quantitative analysis and standardized display. We have determined the intrathoracic location and course of each of the 23 coronary artery segments and branches commonly used for clinical description of disease. Measurements were averaged from perpendicular angiographic view-pairs in 37 patients with normal-sized hearts. Each segment or branch is described by several points along its course; each point is specified in polar coordinates as the radial distance from the principal coronary ostium and by angles about the patient, corresponding to those describing rotation in c-arm radiographic systems. This computer-assisted measurement method is accurate to within +/- 0.2 cm (SD) and +/- 2 degrees in phantom studies. Coronary segment location among a group of normal-sized hearts can be specified to within +/- 1.0 cm (SD). For example, the left anterior descending coronary artery segment at the apex of the heart is 12.2 +/- 1.0 cm from the left coronary ostium, 32 +/- 4 degrees to the left of the anterioposterior axis, and at 46 +/- 7 degrees of caudal angulation. There are several clinically important applications of this new knowledge. First, this anatomic format provides the basis for estimating regional myocardial contraction and the relative size of the myocardial region at risk from a given arterial occlusion. Second, precise knowledge of "normal" segment location greatly simplifies the computation of dimensional correction factors for quantitative arteriography. Third, viewing angles most appropriate for videodensitometric assessment of lesion lumen area may be computed from these data. The theoretical basis and numerical values needed for most of the above estimates are provided. Finally, a computer program has been written to generate a three-dimensional tree-branch vascular model from these anatomic locations. This easily used interactive program aids in teaching coronary angiographic anatomy and, of importance, permits selection of viewing angles that "best" visualize the traditionally difficult parts of the coronary tree.

Intrathoracic spatial location of specified coronary segments on the normal human heart. Applications in quantitative arteriography, assessment of regional risk and contraction, and anatomic display.

J T Dodge

Papers

Lumen diameter of normal human coronary arteries. Influence of age, sex, anatomic variation, and left ventricular hypertrophy or dilation.

Intrathoracic spatial location of specified coronary segments on the normal human heart. Applications in quantitative arteriography, assessment of regional risk and contraction, and anatomic display.