With the advent of multisensor micromanometric/velocimetric catheterization, digital angiography and Doppler and color echocardiography, extensive fluid dynamic quantitation is now possible in cardiology. Such high fidelity instantaneous measurements offer the clinician the prospect of identifying phasic changes in ventricular ejection dynamics that may disclose contraction abnormalities before overt muscle or pump failure is manifested. Accordingly, this review provides a basis for interpreting these measurements and a conceptual framework for understanding ventricular ejection dynamics with and without outflow obstruction. Necessary terminology and fluid dynamic background, including properties of flows generated by large transient forces, Euler and unsteady Bernoulli equations and local and convective acceleration gradients, are reviewed first. Physiologic aspects of ejection dynamics and transvalvular and intraventricular gradients without obstruction are discussed. Maximal outflow acceleration, rather than ejection velocity, coincides with the attainment of the early peak of the nonobstructive pressure gradients. These gradients are characteristically even more asymmetric than are the associated ejection velocity signals. Clinical correlations are introduced, beginning with obstructive transvalvular and subvalvular gradients in aortic stenosis and the phenomenon of recovery of pressure loss in the poststenotic dilation. The large obstructive gradients tend to be distinctively symmetric, as are the ejection waveforms, whose configuration they track more or less closely, depending on the degree of stenosis and relative preponderance of convective effects throughout ejection. Pitfalls in some unwarranted applications of the "simplified Bernoulli equation" are pointed out. Polymorphic gradients of hypertrophic cardiomyopathy, reflecting dynamically dissimilar intraventricular flow regimes in early, mid and late systole, are examined. Enormous late systolic gradients can be associated with progressive shrinkage of flow passage area and sharp increases in linear velocity while volumetric outflow is diminutive. The concept of ventriculoannular disproportion in dilated ventricles is defined and discussed. The implications of ejection fluid dynamics for systolic ventricular and myocardial loading are examined, and the concept of complementarity and competitiveness between intrinsic and extrinsic load components is introduced. Finally, critical research issues are identified and addressed. The primary emphasis is on using the basic principles of fluid dynamics to better understand ejection in the normal or abnormal human left ventricle and aortic root.(ABSTRACT TRUNCATED AT 400 WORDS)

A unique myocardial characteristic is its ability to grow/remodel in order to adapt; this is determined partly by genes and partly by the environment and the milieu intérieur. In the “post-genomic” era, a need is emerging to elucidate the physiologic functions of myocardial genes, as well as potential adaptive and maladaptive modulations induced by environmental/epigenetic factors. Genome sequencing and analysis advances have become exponential lately, with escalation of our knowledge concerning sometimes controversial genetic underpinnings of cardiovascular diseases. Current technologies can identify candidate genes variously involved in diverse normal/abnormal morphomechanical phenotypes, and offer insights into multiple genetic factors implicated in complex cardiovascular syndromes. The expression profiles of thousands of genes are regularly ascertained under diverse conditions. Global analyses of gene expression levels are useful for cataloging genes and correlated phenotypes, and for elucidating the role of genes in maladies. Comparative expression of gene networks coupled to complex disorders can contribute insights as to how “modifier genes” influence the expressed phenotypes. Increasingly, a more comprehensive and detailed systematic understanding of genetic abnormalities underlying, for example, various genetic cardiomyopathies is emerging. Implementing genomic findings in cardiology practice may well lead directly to better diagnosing and therapeutics. There is currently evolving a strong appreciation for the value of studying gene anomalies, and doing so in a non-disjointed, cohesive manner. However, it is challenging for many—practitioners and investigators—to comprehend, interpret, and utilize the clinically increasingly accessible and affordable cardiovascular genomics studies. This survey addresses the need for fundamental understanding in this vital area.

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Functional imaging computational fluid dynamics simulations of right ventricular (RV) inflow fields were obtained by comprehensive software using individual animal-specific dynamic imaging data input from three-dimensional (3-D) real-time echocardiography (RT3D) on a CRAY T-90 supercomputer. Chronically instrumented, lightly sedated awake dogs (n = 7) with normal wall motion (NWM) at control and normal or diastolic paradoxical septal motion (PSM) during RV volume overload were investigated. Up to the E-wave peak, instantaneous inflow streamlines extended from the tricuspid orifice to the RV endocardial surface in an expanding fanlike pattern. During the descending limb of the E-wave, large-scale (macroscopic or global) vortical motions ensued within the filling RV chamber. Both at control and during RV volume overload (with or without PSM), blood streams rolled up from regions near the walls toward the base. The extent and strength of the ring vortex surrounding the main stream were reduced with chamber dilatation. A hypothesis is proposed for a facilitatory role of the diastolic vortex for ventricular filling. The filling vortex supports filling by shunting inflow kinetic energy, which would otherwise contribute to an inflow-impeding convective pressure rise between inflow orifice and the large endocardial surface of the expanding chamber, into the rotational kinetic energy of the vortical motion that is destined to be dissipated as heat. The basic information presented should improve application and interpretation of noninvasive (Doppler color flow mapping, velocity-encoded cine magnetic resonance imaging, etc.) diastolic diagnostic studies and lead to improved understanding and recognition of subtle, flow-associated abnormalities in ventricular dilatation and remodeling.

Epigenetic mechanisms are fundamental in cardiac adaptations, remodeling, reverse remodeling, and disease. This 2-article series proposes that variable forces associated with diastolic RV/LV rotatory intraventricular flows can exert physiologically and clinically important, albeit still unappreciated, epigenetic actions influencing functional and morphological cardiac adaptations and/or maladaptations. Taken in-toto, the 2-part survey formulates a new paradigm in which intraventricular diastolic filling vortex-associated forces play a fundamental epigenetic role, and examines how heart cells react to these forces. The objective is to provide a perspective on vortical epigenetic effects, to introduce emerging ideas and suggest directions of multidisciplinary translational research. The main goal is to make pertinent biophysics and cytomechanical dynamic systems concepts accessible to interested translational and clinical cardiologists. I recognize that the diversity of the epigenetic problems can give rise to a diversity of approaches and multifaceted specialized research undertakings. Specificity may dominate the picture. However, I take a contrasting approach. Are there concepts that are central enough that they should be developed in some detail? Broadness competes with specificity. Would however this viewpoint allow for a more encompassing view that may otherwise be lost by generation of fragmented results? Part 1 serves as a general introduction, focusing on background concepts, on intracardiac vortex imaging methods, and on diastolic filling vortex-associated forces acting epigenetically on RV/LV endocardium and myocardium. Part 2 will describe pertinent available pluridisciplinary knowledge/research relating to mechanotransduction mechanisms for intraventricular diastolic vortex forces and myocardial deformations and to their epigenetic actions on myocardial and ventricular function and adaptations.

We have developed a model for assessing the influence of the decaying contractile systolic tension on diastolic wall dynamics and the passive properties of left ventricular muscle. Total measured left ventricular diastolic pressure and stress (aT) are determined by two overlapping processes: (1) the decay of actively developed pressure and stress (5A) and (2) the buildup of passive filling pressure and stress (C*). The decaying contractile stress aA iS formulated in terms of a relaxation pressure with a time constant (T) assessed during the isovolumic relaxation interval. By subtracting the contribution of aA from aT we obtain 0*. With micromanometry, echocardiography,and cineangiography, total and passive stress-strain relations and strain rates were evaluated over the entire filling period in six normal control subjects and in seven patients with aortic stenosis. Elastic stiffness constants (k), the slopes of the linear passive stiffness vs 0* relations, did not differ in the two groups over a common lower stress range (6/6 normal, k = 9.37 + 1.23; 7/7 aortic stenosis, k = 9.34 + 1.08). Over a higher 0* range, transition into a much steeper linear region occurred, and k values were much larger (4/7 aortic stenosis, k = 28.76 + 2.02). When diastolic stress levels are elevated, passive stiffness-stress relations can be better described as bilinear, with a much greater wall stiffness constant in the higher than in the lower stress range. pected of a purely passively distended elastic chamber has continued to preclude a better understanding of the mechanical behavior of ventricular muscle throughout the entire diastole. In this study we have developed a model for assessing the influence of early incomplete ventricular relaxation on wall dynamics and the passive stiffness of cardiac muscle with data from the entire filling period. MethodsGeneral considerations. The elastic stiffness of intact passive ventricular muscle can be expressed by an incremental modulus concept. Although the overall myocardial stress-strain response curve is nonlinear, it is possible to consider it to be incrementally linear over small successive subranges of stress and strain. Rather than remaining constant, the incremental modulus of passive muscle increases with increasing stress levels, indicating a progressive stiffening of the wall. From the study of Mirsky and Rankin,5 the incremental modulus levels for the wall of a passive elastic chamber are proportional to the ratio of the increment of a stress to the associated increment of a strain. If the measured pressure is used to assess stiffness, this incremental modulus, as well as all other heretofore available stiffness criteria, attains implausible negative values with data from early diastole because passive dynamics are confounded by the decaying contractile wall tension.Definition of passive stress over the entire filling period.

We describe a novel functional imaging approach for quantitative analysis of right ventricular (RV) blood flow patterns in specific experimental animals (or humans) using real-time, three-dimensional (3-D) echocardiography (RT3D). The method is independent of the digital imaging modality used. It comprises three parts. First, a semiautomated segmentation aided by intraluminal contrast medium locates the RV endocardial surface. Second, a geometric scheme for dynamic RV chamber reconstruction applies a time interpolation procedure to the RT3D data to quantify wall geometry and motion at 400 Hz. A volumetric prism method validated the dynamic geometric reconstruction against simultaneous sonomicrometric canine measurements. Finally, the RV endocardial border motion information is used for mesh generation on a computational fluid dynamics solver to simulate development of the early RV diastolic inflow field. Boundary conditions (tessellated endocardial surface nodal velocities) for the solver are directly derived from the endocardial geometry and motion information. The new functional imaging approach may yield important kinematic information on the distribution of instantaneous velocities in the RV diastolic flow field of specific normal or diseased hearts. cardiac image analysis; ventricular function; cardiac fluid dynamics; right ventricle; heart chamber volume QUANTITATIVE ANALYSIS of three-dimensional (3-D) digital cardiac images has become increasingly important given the recent advances in the digital cardiac imaging techniques of 3-D echocardiography, magnetic resonance imaging, computed tomography, and digital fluoroscopy (1,24,26). The growth of these digital imaging techniques is accompanied by an increasing usage of image manipulation tools, providing more elaborate image analysis and measurement and quantitative evaluation and leading to more refined diagnostic accuracy than visual interpretation alone. Moreover, complex mathematical procedures are being used to localize and highlight important changes in cardiac function that cannot be visually detected directly from the original images. With the concurrent development of high-performance computers and analytical software, a functional sort of imaging can now evolve, geared toward the creation of physiological images that are the result of a mathematical simulation derived from a set of images. Such functional imaging will allow visualization and understanding of the evolution of any dynamic process of interest (filling, ejection) within the heart. Accordingly, it should allow better insights into cardiac physiology and pathophysiology and may possibly detect warning signs of diseases not yet overt.This study developed innovative dynamic geometric chamber reconstruction models for use in functional imaging analyses of right ventricular (RV) filling dynamics and physiology. With the use of a new volumetric "prism method," it is first shown that the geometric chamber reconstructions provide accurate and reliable dynamic instantaneous RV chamber geometry ...

We investigated in conscious dogs (a) the effects of heart failure induced by chronic rapid ventricular pacing on the sequence of development of left ventricular (LV) diastolic versus systolic dysfunction and (b) whether the changes were load dependent or secondary to alterations in structure. LV systolic and diastolic dysfunction were evident within 24 h after initiation of pacing and occurred in parallel over 3 wk. LV systolic function was reduced at 3 wk, i.e., peak LV dP/dt fell by -1,327±105 mmHg/s and ejection fraction by -22±2%. LV diastolic dysfunction also progressed over 3 wk of pacing, i.e., r increased by +14.0±2.8 ms and the myocardial stiffness constant by +6.5±1.4, whereas LV chamber stiffness did not change. These alterations were associated with increases in LV endsystolic (+28.6±5.7 g/cm2) and LV end-diastolic stresses (+40.4±53 g/cm2). When stresses and heart rate were matched at the same-levels in the control and failure states, the increases in r and myocardial stiffness were no longer observed, whereas LV systolic function remained depressed. There were no increases in connective tissue content in heart failure. Thus, pacing-induced heart failure in conscious dogs is characterized by major alterations in diastolic function which are reversible with normalization of increased loading condition. (J.