Ares Pasipoularides

Noninvasive assessment of intrinsic ventricular load dynamics in dilated cardiomyopathy

On the basis of hemodynamic theory, a new noninvasive method is developed to provide improved insights into the significance of depressed Doppler left ventricular ejection variables in patients with dilated cardiomyopathy. The net force (F) associated with intraventricular flow throughout ejection can be written as: F = A.dv/dt + B.v2, where v is the ejection velocity and A and B are variables related to the geometry of the ventricle and its outflow tract. Instantaneous levels of this force were calculated in 9 normal subjects and 10 patients with dilated cardiomyopathy using Doppler, M-mode and two-dimensional echocardiography. The maximal ejection force (Fmax) was 47.5 +/- 8.5 kdyn in normal subjects and 25.5 +/- 6.2 kdyn in those with dilated cardiomyopathy (p = 0.0001). Peak local acceleration and outflow velocity were severely depressed in those with cardiomyopathy compared with normal subjects (1,260 +/- 129 versus 2,671 +/- 430 cm/s2 and 71 +/- 14 versus 109 +/- 7 cm/s, respectively; p = 0.0001). Maximal ejection force was attained very early in ejection. A significant linear correlation was found between peak outflow acceleration and maximal ejection force (n = 19; r = 0.91, p = 0.0001). At the time of peak ejection velocity, the net force had decreased to 64% of its peak value in those with cardiomyopathy, whereas in normal subjects, it had decreased to only 84% of its peak value (p = 0.008). In normal subjects, the ejection force was positive during the first 75% of ejection, but in those with cardiomyopathy, it was positive only during the first 54% (p = 0.0003). Once its peak value was attained, total left ventricular systolic wall stress declined rapidly during ejection in normal subjects (to 33% of its peak value by end-ejection), whereas it remained elevated throughout ejection in patients with cardiomyopathy (at 60% of its peak value by end-ejection, p = 0.0001 versus normal). The maximal ejection force corresponded to a calculated intraventricular peak pressure gradient of 9.8 +/- 1.6 mm Hg in normal subjects and 6 +/- 1.2 mm Hg in those with cardiomyopathy (p = 0.0001). The average contribution of the intrinsic component of the left ventricular systolic load (that is, wall stress associated with the ventricular to aortic pressure gradient) to the total myocardial load was 9.1% (range 7.3% to 11.2%) in normal subjects and 6.2% (range 3.9% to 7.5%) in those with cardiomyopathy (p = 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)

Computational fluid dynamics of left ventricular ejection

The present investigation addresses the effects of simple geometric variations on intraventricular ejection dynamics, by methods from computational fluid dynamics. It is an early step in incorporating more and more relevant characteristics of the ejection process, such as a continuously changing irregular geometry, in numerical simulations. We consider the effects of varying chamber eccentricities and outflow valve orifice-to-inner surface area ratios on instantaneous ejection gradients along the axis of symmetry of the left ventricle. The equation of motion for the streamfunction was discretized and solved iteratively with specified boundary conditions on a boundary-fitted adaptive grid, using an alternating-direction-implicit (ADI) algorithm. The unsteady aspects of the ejection process were subsequently introduced into the numerical simulation. It was shown that for given chamber volume and outflow orifice area, higher chamber eccentricities require higher ejection pressure gradients for the same velocity and local acceleration values at the aortic anulus than more spherical shapes. This finding is referable to the rise in local acceleration effects across the outflow axis. This is to be contrasted with the case of outflow orifice stenosis, in which it was shown that it is the convective acceleration effects that are intensified strongly.

Evaluation of right and left ventricular diastolic filling.

A conceptual fluid–dynamics framework for diastolic filling is developed. The convective deceleration load (CDL) is identified as an important determinant of ventricular inflow during the E wave (A wave) upstroke. Convective deceleration occurs as blood moves from the inflow anulus through larger-area cross-sections toward the expanding walls. Chamber dilatation underlies previously unrecognized alterations in intraventricular flow dynamics. The larger the chamber, the larger becomes the endocardial surface and the CDL. CDL magnitude affects strongly the attainable E wave (A wave) peak. This underlies the concept of diastolic ventriculoannular disproportion. Large vortices, whose strength decreases with chamber dilatation, ensue after the E wave peak and impound inflow kinetic energy, averting an inflow-impeding, convective Bernoulli pressure rise. This reduces the CDL by a variable extent depending on vortical intensity. Accordingly, the filling vortex facilitates filling to varying degrees, depending on chamber volume. The new framework provides stimulus for functional genomics research, aimed at new insights into ventricular remodeling.

LV twisting and untwisting in HCM: Ejection begets filling: Diastolic functional aspects of HCM

Conventional and emerging concepts on mechanisms by which hypertrophic cardiomyopathy (HCM) engenders diastolic dysfunction are surveyed. A shift from familiar left ventricular (LV) diastolic function approaches to large-scale (twist-untwist) and small-scale (titin unfolding-refolding, etc.) wall rebound models, incorporating interaction and dynamic distortions and rearrangements of myofiber sheets and ultrastructural constituents, is suggested. Such an emerging new paradigm of diastolic dynamics, emphasizing the relationship of myofiber sheet and ultraconstituent distortion to LV mechanics and end-systolic shape, might clarify intricate patterns of early diastolic rebound and suction, needed for LV filling in many of the polymorphic phenotypes of HCM.

Right and left ventricular diastolic pressure-volume relations: a comprehensive review.

Ventricular compliance alterations can affect cardiac performance and adaptations. Moreover, diastolic mechanics are important in assessing both diastolic and systolic function, since any filling impairment can compromise systolic function. A sigmoidal passive filling pressure–volume relationship, developed using chronically instrumented, awake-animal disease models, is clinically adaptable to evaluating diastolic dynamics using subject-specific micromanometric and volumetric data from the entire filling period of any heartbeat(s). This innovative relationship is the global, integrated expression of chamber geometry, wall thickness, and passive myocardial wall properties. Chamber and myocardial compliance curves of both ventricles can be computed by the sigmoidal methodology over the entire filling period and plotted over appropriate filling pressure ranges. Important characteristics of the compliance curves can be examined and compared between the right and the left ventricle and for different physiological and pathological conditions. The sigmoidal paradigm is more accurate and, therefore, a better alternative to the conventional exponential pressure–volume approximation.

Arterial windkessel parameter estimation: A new time-domain method

We developed and validated a new, more accurate, and easily applied method for calculating the parameters of the three-element Windkessel to quantitate arterial properties and to investigate ventriculoarterial coupling. This method is based on integrating the governing differential equation of the three-element Windkessel and solving for arterial compliance. It accounts for the interaction between characteristic impedance and compliance, an important phenomenon that has been ignored by previously implemented methods. The new integral method was compared with four previously published methods as well as a new independent linear least-squares analysis, using ascending aortic micromanometric and volumetric flow measurements from eight dogs. The parameters calculated by the new integral method were found to be significantly different from those obtained by the previous methods but did not differ significantly from maximum likelihood estimators obtained by a linear leastsquares approach. To assess the accuracy of parameter estimation, pressure and flow waveforms were reconstructed in the time domain by numerically solving the governing differential equation of the three-element Windkessel model. Standard deviations of reconstructed waveforms from the experimental ensemble-averaged waveforms, which solely reflect the relative accuracy of the Windkessel parameters given by the various methods, were calculated. The new integral method invariably yielded the smallest error. These results demonstrate the improved accuracy of our new integral method in estimating arterial parameters of the three-element Windkessel.

Cardiac mechanics: Basic and clinical contemporary research

This survey of cardiac hemodynamics updates evolving concepts of myocardial and ventricular systolic and diastolic loading and function. The pumping action of the heart and its interactions with arterial and venous systems in health and disease provide an extremely rich and challenging field of research, viewed from a fluid dynamic perspective. Many of the more important problems in this field, even if the fluid dynamics in them are considered in isolation, are found to raise questions which have not been asked in the history of fluid dynamics research. Biomedical engineering will increasingly contribute to their solution.

Estimation of the ratio of pulmonary to systemic pressures by pulsed-wave Doppler echocardiography for assessment of pulmonary arterial pressures

This study describes a method for estimation of the ratio of pulmonary to systemic pressures by pulsed-wave Doppler echocardiography. Sixty-eight patients ages 1 day to 68 years who underwent cardiac catheterization had Doppler studies of the right and left ventricular outflows. Preejection period (PEP), ejection time (ET) and mean acceleration to peak velocity (ACCm) were measured on each waveform. The expression: F = (PEP x ACCm)/ET was calculated for right and left ventricular outflows as an index of the effects that the interaction between ventricular contraction and afterload has on the shape of the Doppler waveforms generated in each outflow. The quotient of (F for the right outflow)/(F for the left outflow), or waveform contour ratio, was used to express the degree of pressure-dependent variability between each subjects right and left ventricular outflow tracings. The waveform contour ratio was strikingly similar to the ratio of systolic pulmonary to systemic pressures and also closely correlated to the ratio of mean pressures. The product of waveform contour ratio and arm systolic pressure gave a consistently accurate estimate of systolic pulmonary pressures. It is concluded that the present method can be used successfully for the noninvasive assessment of pulmonary arterial pressures.

Linking Genes to Cardiovascular Diseases: Gene Action and Gene–Environment Interactions

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.

Ejection load changes in aortic stenosis. Observations made after balloon aortic valvuloplasty.

To investigate complementarity and competitiveness between the intrinsic and extrinsic components of the total left ventricular systolic load, hemodynamic data from 18 elderly subjects with severe aortic stenosis were analyzed before and after balloon dilation of the stenosed aortic valve. Multisensor micromanometric pressure measurements allowed calculation (simplified Bernoulli equation) of the ejection velocity and aortic input impedance spectra. Despite a 32% increase in the aortic valve area (from 0.56 +/- 0.04 to 0.74 +/- 0.05 cm2 [mean +/- SEM], p < 0.01), the peak left ventricular systolic pressure fell by only 12% (from 189 +/- 10 to 167 +/- 8 mm Hg, p < 0.01). This was accompanied by an increase in the impedance at the same cardiac output. In a subset of patients (n = 9) in whom the peak aortic systolic pressure rose after valvuloplasty (from 115 +/- 10 to 128 +/- 12 mm Hg, p < 0.01), a 40% increase in the aortic valve area was accompanied by a marked increase in the aortic input impedance. In this subset, the steady component of the aortic input impedance increased by 24% (from 960 +/- 96 to 1,188 +/- 134 dyne.sec/ml, p < 0.05), and the characteristic impedance increased by 25% (from 106 +/- 13 to 132 +/- 19 dyne.sec/ml, p < 0.05). Because of an increased aortic impedance acutely following the procedure, the total left ventricular systolic load after balloon dilation of the stenotic valve was only slightly decreased despite a significant increase in aortic valve area. This represents an example of complementarity and competitiveness between the intrinsic and extrinsic components of the total systolic ventricular load. It may explain why improvement in left ventricular performance may be modest acutely following balloon aortic valvuloplasty.