The association between arterial stiffness and left ventricular filling pressure in an apparently healthy Korean population

Aims

Transesophageal echocardiography (TEE) is the gold standard for the detection of thrombi in patients with atrial fibrillation (AF) before undergoing early electrical cardioversion (CV). However, TEE generates inconclusive results in a considerable number of patients. This study investigated the influence of contrast enhancement on interpretability of TEE for the detection of left atrial (LA) thrombi compared to conventional TEE and assessed, whether there are differences in the rate of thromboembolic events after electrical cardioversion.

Methods

Of 180 patients with AF (51 females, 65.2±13 years) who were referred to CV, 90 were examined with native imaging and contrast enhancement within the same examination (group 1), and 90 were examined with native TEE alone and served as control (group 2). Cineloops of the multiplane examination of the LA and LA appendage (LAA) were stored digitally before and, in group 1, after intravenous bolus application of a transpulmonary contrast agent. Images of group 1 were assessed offline and the diagnosis of LA thrombi was made semi-quantitatively: 1= thrombus present; 2=inconclusive result; 3=no thrombus. The presence of spontaneous echocontrast (SEC) was registered and flow velocity in the LA appendage (LAA-flow) was measured. All patients in whom CV was performed were followed up for 1 year or until relapse of AF. CV related adverse events were defined as any thromboembolic event within 1 week after CV.

Results

No serious adverse events occurred during TEE and contrast enhanced imaging. In group 1 atrial thrombi were diagnosed in 14 (15.6%) during native and in 10 (11.1%) patients during contrast enhanced imaging (p<0.001). Of the 10 patients with thrombi in the contrast TEE group, 7 revealed a decreased LAA-flow (≤0,3m/s) and 8 showed moderate or marked SEC. Uncertain results were significantly more common during native imaging than with contrast enhanced TEE (16 vs. 5 patients, p<0.01). Thrombi could definitely be excluded in 60 (66.7%) during conventional and in 75 patients (83.3%) during contrast enhanced TEE (p<0.01). CV was performed subsequently after exclusion of thrombi and at the discretion of the investigator. In group 1, 74 patients (82.2%) were cardioverted and no patient suffered a CV related complication (p=0.084). In group 2, 76 patients (84.4%) underwent CV, of whom 3 suffered a thromboembolic complication after CV (2 strokes, 1 peripheral embolism).

Conclusion

In patients with AF planned for CV contrast enhancement renders TEE images more interpretable, facilitates the exclusion of atrial thrombi and may reduce the rate of embolic adverse events.     

Wave intensity analysis of left ventricular filling

Wave intensity analysis (WIA) is a powerful technique to study pressure and flow velocity waves in the time domain in vascular networks. The method is based on the analysis of energy transported by the wave through computation of the wave intensity dI = dPdU, where dP and dU denote pressure and flow velocity changes per time interval, respectively. In this study we propose an analytical modification to the WIA so that it can be used to study waves in conditions of time varying elastic properties, such as the left ventricle (LV) during diastole. The approach is first analytically elaborated for a one-dimensional elastic tube-model of the left ventricle with a time-dependent pressure-area relationship. Data obtained with a validated quasi-three dimensional axi-symmetrical model of the left ventricle are employed to demonstrate this new approach. Along the base-apex axis close to the base wave intensity curves are obtained, both using the standard method and the newly proposed modified method. The main difference between the standard and modified wave intensity pattern occurs immediately after the opening of the mitral valve. Where the standard WIA shows a backward expansion wave, the modified analysis shows a forward compression wave. The proposed modification needs to be taken into account when studying left ventricular relaxation, as it affects the wave type.     

Determinants of left ventricular shape change during filling

Left ventricular shape and shape change are easy to measure and their analysis has been proposed as a noninvasive method to determine myocardial anisotropy. In preparation for applying this approach to studies of rats with experimentally induced cardiac hypertrophy, the goals of this study were to describe normal shape changes during diastolic filling in the rat and to utilize a finite-element model to estimate the relative importance of three factors that determine left ventricular shape change during filling: global chamber compliance, fiber to crossfiber stiffness ratio, and fiber architecture. The results suggest that left ventricular shape change is least sensitive to fiber to cross fiber stiffness ratio, and that this will likely limit the practical utility of using shape changes to diagnose changes in myocardial anisotropy.     

Fluid dynamics of the left ventricular filling in dilated cardiomyopathy

Modifications in diastolic function occur in a broad range of cardiovascular diseases and there is an increasing evidence that abnormalities in left ventricular function may contribute significantly to the symptomatology. The flow inside the left ventricle during the diastole is here investigated by numerical solution of the Navier-Stokes equations under the axisymmetric assumption. The equation are written in a body-fitted, moving prolate spheroid, system of coordinates and solved using a fractional step method. The system is forced by a given volume time-law derived from clinical data, and varying the two-degrees-of-freedom ventricle geometry on the basis of a simple model. The solution under healthy conditions is analysed in terms of vorticity dynamics, showing that the flow field is characterised by the presence of a vortex wake; it is attached to the mitral valve during the accelerating phase of the E-wave, and it detaches and translate towards the ventricle apex afterwards. The flow evolution is discussed, results are also reported as an M-mode representation of colour-coded Doppler velocity maps. In the presence of ventricle dilatation the mitral jet extends farther inside the ventricle, propagation velocity decreases, and the fluid stagnates longer at the apex.     

Estimation of the left ventricular relaxation time constant tau requires consideration of the pressure asymptote

The left ventricular isovolumic pressure decay, obtained by cardiac catheterization, is widely characterized by the time constant tau of the exponential regression p(t)=Pomega+(P0-Pomega)exp(-t/tau). However, several authors prefer to prefix Pomega=0 instead of coestimating the pressure asymptote empirically; others present tau values estimated by both methods that often lead to discordant results and interpretation of lusitropic changes. The present study aims to clarify the relations between the tau estimates from both methods and to decide for the more reliable estimate. The effect of presetting a zero asymptote on the tau estimate was investigated mathematically and empirically, based on left ventricular pressure decay data from isolated ejecting rat and guinea pig hearts at different preload and during spontaneous decrease of cardiac function. Estimating tau with preset Pomega=0 always yields smaller values than the regression with empirically estimated asymptote if the latter is negative and vice versa. The sequences of tau estimates from both methods can therefore proceed in reverse direction if tau and Pomega change in opposite directions between the measurements. This is exemplified by data obtained during an increasing preload in spontaneously depressed isolated hearts. The estimation of the time constant of isovolumic pressure fall with a preset zero asymptote is heavily biased and cannot be used for comparing the lusitropic state of the heart in hemodynamic conditions with considerably altered pressure asymptotes.     

Developmental changes in left and right ventricular diastolic filling patterns in mice

Developmental changes in left and right ventricular diastolic filling patterns were determined noninvasively in isoflurane-anesthetized outbred ICR mice. Blood velocities in the mitral and tricuspid orifices were recorded in 16 embryos at days 14.5 (E14.5) and 17.5 of gestation (E17.5) using an ultrasound biomicroscope and also serially in three groups of postnatal mice aged 1-7 days (n = 23), 1-4 wk (n = 18), and 4-12 wk (n = 27) using 20-MHz pulsed Doppler. Postnatal body weight increased rapidly to 8 wk. Heart rate increased rapidly from approximately 180 beats/min at E14.5 to approximately 380 beats/min at 1 wk after birth and then more gradually to plateau at approximately 450 beats/min after 4 wk. Ventricular filling was quantified using the ratio of peak velocity of early ventricular filling due to active relaxation (E wave) to that of the late ventricular filling caused by atrial contraction (A wave) (peak E/A ratio) and the ratio of the peak E velocity to total time-velocity integral of E and A waves (peak E/total TVI ratio). Both ventricles had similar diastolic filling patterns in embryos (peak E/A ratio of 0.28 +/- 0.02 for mitral flow and 0.27 +/- 0.02 for tricuspid flow at E14.5). After birth, mitral peak E/A increased to >1 between the third and fifth day, continued to increase to 2.25 +/- 0.25 at approximately 3 wk, and then remained stable. The tricuspid peak E/A ratio increased much less but stabilized at the same age (increased to 0.79 +/- 0.03 at 3 wk). The peak E/total TVI ratio showed similar left-right differences and changes with development. Age-related changes were largely due to increases in peak E velocity. The results suggest that diastolic function matures approximately 3 wk postnatally, presumably in association with maturation of ventricular recoil and relaxation mechanisms.     

Impaired left ventricular filling due to right-to-left ventricular interaction in patients with pulmonary arterial hypertension

The aim of this study was to investigate the contribution of direct right-to-left ventricular interaction to left ventricular filling and stroke volume in 46 patients with pulmonary arterial hypertension (PAH) and 18 control subjects. Stroke volume, right and left ventricular volumes, left ventricular filling rate, and interventricular septum curvature were measured by magnetic resonance imaging and left atrial filling by transesophageal echocardiography. Stroke volume, left ventricular end-diastolic volume, and left ventricular peak filling rate were decreased in PAH patients compared with control subjects: 28 +/- 13 vs. 41 +/- 10 ml/m(2) (P < 0.001), 46 +/- 14 vs. 61 +/- 14 ml/m(2) (P < 0.001), and 216 +/- 90 vs. 541 +/- 248 ml/s (P < 0.001), respectively. Among PAH patients, stroke volume did not correlate to right ventricular end-diastolic volume or mean pulmonary arterial pressure but did correlate to left ventricular end-diastolic volume (r = 0.62, P < 0.001). Leftward interventricular septum curvature was correlated to left ventricular filling rate (r = 0.64, P < 0.001) and left ventricular end-diastolic volume (r = 0.65, P < 0.001). In contrast, left atrial filling was normal and not correlated to left ventricular end-diastolic volume. In PAH patients, ventricular interaction mediated by the interventricular septum impairs left ventricular filling, contributing to decreased stroke volume.     

Relation of arterial stiffness to left ventricular structure and function in healthy women

Background

Interactions between the left ventricular (LV) and the arterial system, (ventricular-arterial coupling) are key determinants of cardiovascular function. However, most of studies covered multiple cardiovascular risk factors, which also contributed to the morphological and functional changes of LV. The aim of this study was to examine the relationship between arterial stiffness and LV structure and function in healthy women with a low burden of risk factors.

Methods

Healthy women from the Twins UK cohort (n?=?147, mean age was 54.07?±?11.90 years) were studied. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cf-PWV). LV structure and function were assessed by two-dimensional speckle tracking echocardiography.

Results

cf-PWV was significantly associated with most measures of LV geometry and function, including relative wall thickness (RWT), E/e’ ratio, global circumferential and radial strain, apical rotation and LV twist (each p?<? 0.05), but bore no relation to global longitudinal strain. After adjustment for age, body mass index, blood pressure and heart rate, cf-PWV was significantly correlated with RWT, global circumferential strain, apical rotation and LV twist (β?=?0.011, ??0.484, 1.167 and 1.089, respectively, each p?≤? 0.05).

Conclusions

In healthy women with a low burden of risk factors, elevated arterial stiffness was intimately interwoven with increased LV twisting even before LV dysfunction becomes clinically evident.

     

Chamber properties from transmitral flow: prediction of average and passive left ventricular diastolic stiffness.

A chamber stiffness (K(LV))-transmitral flow (E-wave) deceleration time relation has been invasively validated in dogs with the use of average stiffness [(DeltaP/DeltaV)(avg)]. K(LV) is equivalent to k(E), the (E-wave) stiffness of the parameterized diastolic filling model. Prediction and validation of 1) (DeltaP/DeltaV)(avg) in terms of k(E), 2) early rapid-filling stiffness [(DeltaP/DeltaV)(E)] in terms of k(E), and 3) passive (postdiastasis) chamber stiffness [(DeltaP/DeltaV)(PD)] from A waves in terms of the stiffness parameter for the Doppler A wave (k(A)) have not been achieved. Simultaneous micromanometric left ventricular (LV) pressure (LVP) and transmitral flow from 131 subjects were analyzed. (DeltaP)(avg) and (DeltaV)(avg) utilized the minimum LVP-LV end-diastolic pressure interval. (DeltaP/DeltaV)(E) utilized DeltaP and DeltaV from minimum LVP to E-wave termination. (DeltaP/DeltaV)(PD) utilized atrial systolic DeltaP and DeltaV. E- and A-wave analysis generated k(E) and k(A). For all subjects, noninvasive-invasive relations yielded the following equations: k(E) = 1,401. (DeltaP/DeltaV)(avg) + 59.2 (r = 0.84) and k(E) = 229.0. (DeltaP/DeltaV)(E) + 112 (r = 0.80). For subjects with diastasis (n = 113), k(A) = 1,640. (DeltaP/DeltaV)(PD) - 8.40 (r = 0.89). As predicted, k(A) showed excellent correlation with (DeltaP/DeltaV)(PD); k(E) correlated highly with (DeltaP/DeltaV)(avg). In vivo validation of average, early, and passive chamber stiffness facilitates quantitative, noninvasive diastolic function assessment from transmitral flow.     

Influence of the pericardium on right and left ventricular filling in the dog

We compared the influence of the pericardium on left and right ventricular (LV, RV) filling by measuring LV and RV pressures and segment lengths (SL, LV free wall, and RV inflow and outflow tracts) in six open-chest, pentobarbital sodium-anesthetized dogs before and after pericardiectomy. End-diastolic pressure (EDP) was varied by partial caval occlusion and dextran infusion. At each site the ln EDP-SL relation was fitted by linear regression and characterized by its slope and 1-Torr EDP intercept. The slope and 1-Torr intercept of the LV ln EDP-SL relation changed variably after pericardiectomy, but in each dog a change occurred that shifted this relation downward. In contrast, the RV inflow tract slope invariably decreased significantly after pericardiectomy, whereas its intercept was unchanged in all but one dog. The RV outflow tract results were similar to the inflow tract but less consistent. By the use of the raw EDP-SL data points, we calculated that the absolute contribution of the pericardium to EDP (i.e., the effective pericardial surface pressure) was similar at the three sites. However, as EDP values increased the proportional contribution of the pericardium to right ventricular end-diastolic pressure (RVEDP) increased, whereas that to left ventricular end-diastolic pressure (LVEDP) remained relatively constant. As a result, at the higher EDP values tested, the pericardium was responsible for a larger proportion of RVEDP than LVEDP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Wave intensity analysis of left ventricular filling: application of windkessel theory

We extend our recently published windkessel-wave interpretation of vascular function to the wave intensity analysis (WIA) of left ventricular (LV) filling dynamics by separating the pressure changes due to the windkessel from those due to traveling waves. With the use of LV compliance, the change in pressure due solely to LV volume changes (windkessel pressure) can be isolated. Inasmuch as the pressure measured in the cardiovascular system is the sum of its windkessel and wave components (excess pressure), it can be substituted into WIA, yielding the isolated wave effects on LV filling. Our study of six open-chest dogs demonstrated that once the windkessel effects are removed from WIA, the energy of diastolic suction is 2.6 times greater than we previously calculated. Volume-related changes in pressure (i.e., the windkessel or reservoir effect) must be considered first when wave motion is analyzed.     

Model and influence of mitral valve opening during the left ventricular filling

The flow inside a model left ventricle during filling (diastole) is simulated by the numerical solution of the equations of motion under the axisymmetric approximation. The left ventricle is taken with a truncated ellipsoid geometry, and a simple conceptual model is introduced to simulate the presence of the moving mitral valve. A relevant role during the left ventricle diastolic flow, as already discussed by other authors, is played by the travelling vortex wake that is formed from the transmitral jet during the early filling acceleration phase. The presence of a moving valve is found to produce a non-simultaneous spatial development of the entering bulk flow and a slightly more complex vortex wake structure; the results are discussed in comparison with fixed valve ones. They are analysed also in terms of M-mode representation suggesting a physical interpretation of the pattern detected in the clinical measurements that extends the one given previously on the basis of fixed valve models.     

Doppler echocardiographic estimation of left ventricular end-diastolic pressure after MI in rats

The spectral Doppler mitral flow pattern, alone or combined with tissue Doppler mitral annulus velocity, can be used to predict left ventricular (LV) filling pressure in humans, whereas invasive hemodynamic measurements are still required in the rat. This study was undertaken to assess whether LV end-diastolic pressure (LVEDP) can be estimated using Doppler echocardiography in the rat after myocardial infarction (MI). Thirty-seven rats (23 rats with MI after left coronary artery ligation and 14 sham-operated rats) were evaluated 3 mo after surgery with echo-Doppler and invasive hemodynamic measurements. Pulse wave spectral Doppler at the mitral valve tip was used to measure the E wave, the E wave deceleration time (DT), and the A wave; spectral Doppler tissue imaging was used to measure the early diastolic lateral mitral annulus velocity (E(a)). We found weak correlations between LVEDP and the peak velocity of the early mitral inflow (E), E/peak velocity of the late mitral inflow, and DT, and strong correlations with E(a) and especially with E/E(a) [R(2) = 0.89, LVEDP (in mmHg) = 0.987E/E(a) - 4.229]. Longitudinal followup of a subgroup of rats with MI revealed a marked rise of E/E(a) between days 7 and 21 in rats with heart failure only. We conclude that Doppler echocardiography can be used for serial assessment of LV diastolic function in rats with MI.     

Role of impaired myocardial relaxation in the production of elevated left ventricular filling pressure

Although present in many patients with heart failure and a normal ejection fraction, the role of isolated impairments in active myocardial relaxation in the genesis of elevated filling pressures is not well characterized. Because of difficulties in determining the effect of prolonged myocardial relaxation in vivo, we used a cardiovascular simulated computer model. The effect of myocardial relaxation, as assessed by tau (exponential time constant of relaxation), on pulmonary vein pressure (PVP) and left ventricular end-diastolic pressure (LVEDP) was investigated over a wide range of tau values (20-100 ms) and heart rate (60-140 beats/min) while keeping end-diastolic volume constant. Cardiac output was recorded over a wide range of tau and heart rate while keeping PVP constant. The effect of systolic intervals was investigated by changing time to end systole at the same heart rate. At a heart rate of 60 beats/min, increases in tau from a baseline to extreme value of 100 ms cause only a minor increase in PVP of 3 mmHg. In contrast, at 120 beats/min, the same increase in tau increases PVP by 23 mmHg. An increase in filling pressures at high heart rates was attributable to incomplete relaxation. The PVP-LVEDP gradient was not constant and increased with increasing tau and heart rate. Prolonged systolic intervals augmented the effects of tau on PVP. Impaired myocardial relaxation is an important determinant of PVP and cardiac output only during rapid heart rate and especially when combined with prolonged systolic intervals. These findings clarify the role of myocardial relaxation in the pathogenesis of elevated filling pressures characteristic of heart failure.     

Multiphysics simulation of left ventricular filling dynamics using fluid-structure interaction finite element method

To relate the subcellular molecular events to organ level physiology in heart, we have developed a three-dimensional finite-element-based simulation program incorporating the cellular mechanisms of excitation-contraction coupling and its propagation, and simulated the fluid-structure interaction involved in the contraction and relaxation of the human left ventricle. The FitzHugh-Nagumo model and four-state model representing the cross-bridge kinetics were adopted for cellular model. Both ventricular wall and blood in the cavity were modeled by finite element mesh. An arbitrary Lagrangian Eulerian finite element method with automatic mesh updating has been formulated for large domain changes, and a strong coupling strategy has been taken. Using electrical analog of pulmonary circulation and left atrium as a preload and the windkessel model as an afterload, dynamics of ventricular filling as well as ejection was simulated. We successfully reproduced the biphasic filling flow consisting of early rapid filling and atrial contraction similar to that reported in clinical observation. Furthermore, fluid-structure analysis enabled us to analyze the wave propagation velocity of filling flow. This simulator can be a powerful tool for establishing a link between molecular abnormality and the clinical disorder at the macroscopic level.     

The effect of vortex formation on left ventricular filling and mitral valve efficiency

A new mechanism for quantifying the filling energetics in the left ventricle (LV) and past mechanical heart valves (MHV) is identified and presented. This mechanism is attributed to vortex formation dynamics past MHV leaflets. Recent studies support the conjecture that the natural healthy left ventricle (LV) performs in an optimum, energy-preserving manner by redirecting the flow with high efficiency. Yet to date, no quantitative proof has been presented. The present work provides quantitative results and validation of a theory based on the dynamics of vortex ring formation, which is governed by a critical formation number (FN) that corresponds to the dimensionless time at which the vortex ring has reached its maximum circulation content, in support of this hypothesis. Herein, several parameters (vortex ring circulation, vortex ring energy, critical FN, hydrodynamic efficiencies, vortex ring propagation speed) have been quantified and presented as a means of bridging the physics of vortex formation in the LV. In fact, the diastolic hydrodynamic efficiencies were found to be 60, 41, and 29%, respectively, for the porcine, anti-anatomical, and anatomical valve configurations. This assessment provides quantitative proof of vortex formation, which is dependent of valve design and orientation, being an important flow characteristic and associated to LV energetics. Time resolved digital particle image velocimetry with kilohertz sampling rate was used to study the ejection of fluid into the LV and resolve the spatiotemporal evolution of the flow. The clinical significance of this study is quantifying vortex formation and the critical FN that can potentially serve as a parameter to quantify the LV filling process and the performance of heart valves.     

ACE and AGTR1 genes polymorphisms in left ventricular hypertrophy pathogenesis in humans

The role of A2350G polymorphism in exon 17 of the ACE gene and A1166C - in 3'-UTR of the AGTR1 in the pathogenesis of left ventricular hypertrophy was studied in patients with essential hypertension (EH) and arterial hypertension combined with diabetes mellitus type 2 (AH + DM2). Patients with EH and AH + DM2 did not differ from the control sample of healthy individuals by allele or genotype frequencies. However, an association of both polymorphisms with LVH was detected in EH patients. The frequency of 1166C allele was higher in patients with LVH (33.6% vs 20.7% without LVH). A1166C polymorphism determined the magnitude of left ventricular mass index (LVMI) in EH patients as well (p = 0.007). 2350G allele frequency of the ACE gene was in 1.5, and GG genotype--in 3.5-fold higher in EH patients with LVH, as compared without LVH. LVMI was significantly higher in patients with GG genotype as compared with heterozygotes and AA homozygotes (p = 0.002). Thus the presence of 1166C allele of AGTR1 and 2350G allele of ACE can be considered as predisposing factors for LVH development in EH. In contrast, association of studied polymorphisms with presence or LVH degree was not detected in patients with arterial hypertension combined with DM2. This may indicate another structure of genetic component of predisposition to LVH in different causes.