Pablo Martinez-Legazpi

Contribution of the Diastolic Vortex Ring to Left Ventricular Filling

BACKGROUND Intraventricular fluid dynamics can be assessed clinically using imaging. The contribution of vortex structures to left ventricular (LV) diastolic function has never been quantified in vivo. OBJECTIVES This study sought to understand the impact of intraventricular flow patterns on filling and to assess whether impaired fluid dynamics may be a source of diastolic dysfunction. METHODS Two-dimensional flow velocity fields from color Doppler echocardiographic sequences were obtained in 20 patients with nonischemic dilated cardiomyopathy (NIDCM), 20 patients with hypertrophic cardiomyopathy (HCM), and 20 control healthy volunteers. Using a flow decomposition method, we isolated the rotational velocity generated by the vortex ring from the surrounding flow in the left ventricle. RESULTS The vortex was responsible for entering 13 ± 6% of filling volume in the control group and 19 ± 8% in the NIDCM group (p = 0.004), but only 5 ± 5% in the HCM group (p < 0.0001 vs. controls). Favorable vortical effects on intraventricular pressure gradients were observed in the control and NIDCM groups but not in HCM patients. Differences in chamber sphericity explained variations in the vortex contribution to filling between groups (p < 0.005). CONCLUSIONS The diastolic vortex is responsible for entering a significant fraction of LV filling volume at no energetic or pressure cost. Thus, intraventricular fluid mechanics are an important determinant of global chamber LV operative stiffness. Reduced stiffness in NIDCM is partially related to enhanced vorticity. Conversely, impaired vortex generation is an unreported mechanism of diastolic dysfunction in HCM and probably other causes of concentric remodeling.

Systemic vascular load in calcific degenerative aortic valve stenosis: insight from percutaneous valve replacement.

BACKGROUND Systemic arterial load impacts the symptomatic status and outcome of patients with calcific degenerative aortic stenosis (AS). However, assessing vascular properties is challenging because the arterial trees behavior could be influenced by the valvular obstruction. OBJECTIVES This study sought to characterize the interaction between valvular and vascular functions in patients with AS by using transcatheter aortic valve replacement (TAVR) as a clinical model of isolated intervention. METHODS Aortic pressure and flow were measured simultaneously using high-fidelity sensors in 23 patients (mean 79 ± 7 years of age) before and after TAVR. Blood pressure and clinical response were registered at 6-month follow-up. RESULTS Systolic and pulse arterial pressures, as well as indices of vascular function (vascular resistance, aortic input impedance, compliance, and arterial elastance), were significantly modified by TAVR, exhibiting stiffer vascular behavior post-intervention (all, p < 0.05). Peak left ventricular pressure decreased after TAVR (186 ± 36 mm Hg vs. 162 ± 23 mm Hg, respectively; p = 0.003) but remained at >140 mm Hg in 70% of patients. Wave intensity analysis showed abnormally low forward and backward compression waves at baseline, increasing significantly after TAVR. Stroke volume decreased (-21 ± 19%; p < 0.001) and correlated with continuous and pulsatile indices of arterial load. In the 48 h following TAVR, a hypertensive response was observed in 12 patients (52%), and after 6-month follow-up, 5 patients required further intensification of discharge antihypertensive therapy. CONCLUSIONS Vascular function in calcific degenerative AS is conditioned by the upstream valvular obstruction that dampens forward and backward compression waves in the arterial tree. An increase in vascular load after TAVR limits the procedures acute afterload relief.

Intraventricular vortex properties in nonischemic dilated cardiomyopathy

Vortices may have a role in optimizing the mechanical efficiency and blood mixing of the left ventricle (LV). We aimed to characterize the size, position, circulation, and kinetic energy (KE) of LV main vortex cores in patients with nonischemic dilated cardiomyopathy (NIDCM) and analyze their physiological correlates. We used digital processing of color-Doppler images to study flow evolution in 61 patients with NIDCM and 61 age-matched control subjects. Vortex features showed a characteristic biphasic temporal course during diastole. Because late filling contributed significantly to flow entrainment, vortex KE reached its maximum at the time of the peak A wave, storing 26 ± 20% of total KE delivered by inflow (range: 1-74%). Patients with NIDCM showed larger and stronger vortices than control subjects (circulation: 0.008 ± 0.007 vs. 0.006 ± 0.005 m(2)/s, respectively, P = 0.02; KE: 7 ± 8 vs. 5 ± 5 mJ/m, P = 0.04), even when corrected for LV size. This helped confining the filling jet in the dilated ventricle. The vortex Reynolds number was also higher in the NIDCM group. By multivariate analysis, vortex KE was related to the KE generated by inflow and to chamber short-axis diameter. In 21 patients studied head to head, Doppler measurements of circulation and KE closely correlated with phase-contract magnetic resonance values (intraclass correlation coefficient = 0.82 and 0.76, respectively). Thus, the biphasic nature of filling determines normal vortex physiology. Vortex formation is exaggerated in patients with NIDCM due to chamber remodeling, and enlarged vortices are helpful for ameliorating convective pressure losses and facilitating transport. These findings can be accurately studied using ultrasound.

Validation of Noninvasive Indices of Global Systolic Function in Patients With Normal and Abnormal Loading Conditions A Simultaneous Echocardiography Pressure-Volume Catheterization Study

Background—Noninvasive indices based on Doppler echocardiography are increasingly used in clinical cardiovascular research to evaluate left ventricular global systolic chamber function. Our objectives were to clinically validate ultrasound-based methods of global systolic chamber function to account for differences between patients in conditions of abnormal load, and to assess their sensitivity to load confounders. Methods and Results—Twenty-seven patients (8 dilated cardiomyopathy, 10 normal ejection fraction, and 9 end-stage liver disease) underwent simultaneous echocardiography and left heart catheterization with pressure-conductance instrumentation. The reference index, maximal elastance (Emax), was calculated from pressure–volume loop data obtained during acute inferior vena cava occlusion. A wide range of values were observed for left ventricular systolic chamber function (Emax: 2.8±1.0 mm Hg/mL), preload, and afterload. Among the noninvasive indices tested, the peak ejection intraventricular pressure difference showed the best correlation with Emax (R=0.75). A significant but weaker correlation with Emax was observed for ejection fraction (R=0.41), midwall fractional shortening (R=0.51), global circumferential strain (R=−0.53), and strain rate (R=−0.46). Longitudinal strain and strain rate failed to correlate with Emax, as did noninvasive single-beat estimations of this index. Principal component and multiple regression analyses demonstrated that peak ejection intraventricular pressure difference was less sensitive to load, whereas ejection fraction and longitudinal strain and strain rate were heavily influenced by afterload. Conclusions—Current ultrasound methods have limited accuracy to characterize global left ventricular systolic chamber function in a given patient. The Doppler-derived peak ejection intraventricular pressure difference should be preferred for this purpose because it best correlates with the reference index and is more robust in conditions of abnormal load.

Diastolic chamber properties of the left ventricle assessed by global fitting of pressure-volume data: improving the gold standard of diastolic function

In cardiovascular research, relaxation and stiffness are calculated from pressure-volume (PV) curves by separately fitting the data during the isovolumic and end-diastolic phases (end-diastolic PV relationship), respectively. This method is limited because it assumes uncoupled active and passive properties during these phases, it penalizes statistical power, and it cannot account for elastic restoring forces. We aimed to improve this analysis by implementing a method based on global optimization of all PV diastolic data. In 1,000 Monte Carlo experiments, the optimization algorithm recovered entered parameters of diastolic properties below and above the equilibrium volume (intraclass correlation coefficients = 0.99). Inotropic modulation experiments in 26 pigs modified passive pressure generated by restoring forces due to changes in the operative and/or equilibrium volumes. Volume overload and coronary microembolization caused incomplete relaxation at end diastole (active pressure > 0.5 mmHg), rendering the end-diastolic PV relationship method ill-posed. In 28 patients undergoing PV cardiac catheterization, the new algorithm reduced the confidence intervals of stiffness parameters by one-fifth. The Jacobian matrix allowed visualizing the contribution of each property to instantaneous diastolic pressure on a per-patient basis. The algorithm allowed estimating stiffness from single-beat PV data (derivative of left ventricular pressure with respect to volume at end-diastolic volume intraclass correlation coefficient = 0.65, error = 0.07 ± 0.24 mmHg/ml). Thus, in clinical and preclinical research, global optimization algorithms provide the most complete, accurate, and reproducible assessment of global left ventricular diastolic chamber properties from PV data. Using global optimization, we were able to fully uncouple relaxation and passive PV curves for the first time in the intact heart.

The role of elastic restoring forces in right ventricular filling

AIMS The physiological determinants of RV diastolic function remain poorly understood. We aimed to quantify the contribution of elastic recoil to RV filling and determine its sensitivity to interventricular interaction. METHODS AND RESULTS High-fidelity pressure-volume loops and simultaneous 3-dimensional ultrasound sequences were obtained in 13 pigs undergoing inotropic modulation, volume overload, and acute pressure overload induced by endotoxin infusion. Using a validated method, we isolated elastic restoring forces from ongoing relaxation using conventional pressure-volume data. The RV contracted below the equilibrium volume in >75% of the data sets. Consequently, elastic recoil generated strong sub-atmospheric passive pressure at the onset of diastole [-3 (-4 to -2) mmHg at baseline]. Stronger restoring suction pressure was related to a shorter isovolumic relaxation period, a higher rapid filling fraction, and lower atrial pressures (all P < 0.05). Restoring forces were mostly determined by the position of operating volumes around the equilibrium volume. By this mechanism, the negative inotropic effect of beta-blockade reduced and sometimes abolished restoring forces. During acute pressure overload, restoring forces initially decreased, but recovered at advanced stages. This biphasic response was related to alterations of septal curvature induced by changes in the diastolic LV-RV pressure balance. The constant of elastic recoil was closely related to the constant of passive stiffness (R = 0.69). CONCLUSION The RV works as a suction pump, exploiting contraction energy to facilitate filling by means of strong elastic recoil. Restoring forces are influenced by the inotropic state and RV conformational changes mediated by direct ventricular interdependence.

How heavy is the load? The ventricular mechanics of mitral regurgitation revisited in the era of percutaneous therapies

The impact of mitral regurgitation (MR) on left ventricular (LV) function and remodelling has been typically described in terms of a pure volume overload. In fact, LV afterload in MR is sometimes believed to be below normal ‘because the regurgitant orifice allows blood to exit the ventricle with little opposition’. Moreover, this argument sometimes is followed by the idea that a low-afterload leads to overestimate intrinsic LV systolic function in MR. Remarkably, despite a number of authors have emphasised that afterload is not reduced in chronic MR,1 ,2 the idea is still prevalent. Describing MR merely as a volume overload condition also overlooks other biomechanical consequences of MR, which deserve discussion. The LV is capable of maintaining stroke volume in chronic MR until advanced stages of the disease because, following the Frank-Starling law, diastolic lengthening increases shortening of the sarcomere. If the regurgitant leak were unrestrictive, this compensating mechanism would be insufficient to maintain forward flow because the preload-recruited stroke volume would be mostly pumped towards the left atrium. In chronic MR, the regurgitant lesion always imposes a significant opposition to backflow. Although its area may vary during systole, in fluid-mechanical terms, the regurgitant lesion in MR behaves as a small, flat and restrictive orifice. Very large free regurgitant lesions, as sometimes found in severe tricuspid insufficiency—showing a laminar regurgitant flow and a very low transtricuspid pressure gradient—are virtually never seen in chronic MR. Furthermore, even in advanced stages of the disease, any decline in cardiac output is compensated by vasomotor reflexes. Consequently, systolic blood pressure remains normal in chronic MR.1 Ventricular pressure translates to afterload by means of wall-stress. Governed by Laplaces law, systolic wall-stress is directly proportional to systolic LV pressure. But systolic wall-stress is also directly proportional to the degree of wall curvature (radius), …

Stasis Mapping Using Ultrasound: A Prospective Study in Acute Myocardial Infarction

During the subacute phase of acute myocardial infarction (AMI), the incidence of left ventricular thrombosis (LVT) can be as high as 15% to 20%. A method for assessing the risk of LVT would be of particular value in the setting of AMI, because prophylactic anticoagulation must be balanced against

ABNORMAL EXERCISE HEMODYNAMICS IN PATIENTS WITH LOW GRADIENT AORTIC STENOSIS AND PRESERVED EJECTION FRACTION: A SIMULTANEOUS STRESS ECHO-RIGHT HEART CATHETERIZATION STUDY

The systemic arterial load modulates the clinical impact of aortic stenosis (AS). The hemodynamic response to exercise has never been measured invasively in patients with low-gradient (LG) AS and normal ejection fraction. Twenty patients (77 ± 6 years old; 17 female) with LGAS (mean pressure