Vascular Elastance Research Articles

Mechanisms maintaining right ventricular contractility-to-pulmonary arterial elastance ratio in VA ECMO: a retrospective animal data analysis of RV–PA coupling

BackgroundTo optimize right ventricular–pulmonary coupling during veno-arterial (VA) ECMO weaning, inotropes, vasopressors and/or vasodilators are used to change right ventricular (RV) function (contractility) and pulmonary artery (PA) elastance (afterload). RV–PA coupling is the ratio between right ventricular contractility and pulmonary vascular elastance and as such, is a measure of optimized crosstalk between ventricle and vasculature. Little is known about the physiology of RV–PA coupling during VA ECMO. This study describes adaptive mechanisms for maintaining RV–PA coupling resulting from changing pre- and afterload conditions in VA ECMO.MethodsIn 13 pigs, extracorporeal flow was reduced from 4 to 1 L/min at baseline and increased afterload (pulmonary embolism and hypoxic vasoconstriction). Pressure and flow signals estimated right ventricular end-systolic elastance and pulmonary arterial elastance. Linear mixed-effect models estimated the association between conditions and elastance.ResultsAt no extracorporeal flow, end-systolic elastance increased from 0.83 [0.66 to 1.00] mmHg/mL at baseline by 0.44 [0.29 to 0.59] mmHg/mL with pulmonary embolism and by 1.36 [1.21 to 1.51] mmHg/mL with hypoxic pulmonary vasoconstriction (p < 0.001). Pulmonary arterial elastance increased from 0.39 [0.30 to 0.49] mmHg/mL at baseline by 0.36 [0.27 to 0.44] mmHg/mL with pulmonary embolism and by 0.75 [0.67 to 0.84] mmHg/mL with hypoxic pulmonary vasoconstriction (p < 0.001). Coupling remained unchanged (2.1 [1.8 to 2.3] mmHg/mL at baseline; − 0.1 [− 0.3 to 0.1] mmHg/mL increase with pulmonary embolism; − 0.2 [− 0.4 to 0.0] mmHg/mL with hypoxic pulmonary vasoconstriction, p > 0.05). Extracorporeal flow did not change coupling (0.0 [− 0.0 to 0.1] per change of 1 L/min, p > 0.05). End-diastolic volume increased with decreasing extracorporeal flow (7.2 [6.6 to 7.8] ml change per 1 L/min, p < 0.001).ConclusionsThe right ventricle dilates with increased preload and increases its contractility in response to afterload changes to maintain ventricular–arterial coupling during VA extracorporeal membrane oxygenation.

Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Arterial Stiffness and Abnormal Left Ventricular Hemodynamic Responses During Exercise

BackgroundArterial stiffness is thought to contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF). We sought to examine arterial stiffness in HFpEF and hypertension and investigate associations of arterial and left ventricular hemodynamic responses to exercise. Methods and ResultsA total of 385 symptomatic individuals with an EF of ≥50% underwent upright cardiopulmonary exercise testing with invasive hemodynamic assessment of arterial stiffness and load (aortic augmentation pressure, augmentation index, systemic vascular resistance index, total arterial compliance index, effective arterial elastance index, and pulse pressure amplification) at rest and during incremental exercise. An abnormal hemodynamic response to exercise was defined as a steep increase in pulmonary capillary wedge pressure relative to cardiac output (∆PCWP/∆CO > 2 mm Hg/L/min). We compared rest and exercise measures between HFpEF and hypertension in multivariable analyses. Among 188 participants with HFpEF (mean age 61 ± 13 years, 56% women), resting arterial stiffness parameters were worse compared with 94 hypertensive participants (mean age 55 ± 15 years, 52% women); these differences were accentuated during exercise in HFpEF (all P ≤ .0001). Among all participants, exercise measures of arterial stiffness correlated with worse ∆PCWP/∆CO. Specifically, a 1 standard deviation higher exercise augmentation pressure was associated with 2.15-fold greater odds of abnormal LV hemodynamic response (95% confidence interval 1.52–3.05; P < .001). Further, exercise measures of systemic vascular resistance index, elastance index, and pulse pressure amplification correlated with a lower peak oxygen consumption. ConclusionsExercise accentuates the increased arterial stiffness found in HFpEF, which in turn correlates with left ventricular hemodynamic responses. Unfavorable ventricular–vascular interactions during exercise in HFpEF may contribute to exertional intolerance and inform future therapeutic interventions.

Acute Unloading Effects of Sildenafil Enhance Right Ventricular–Pulmonary Artery Coupling in Heart Failure

BackgroundPhosphodiesterase-5A inhibitors (PDE5i) are sometimes used in patients with advanced heart failure with reduced ejection fraction before heart transplant or left ventricular assist device implantation to decrease right ventricular (RV) afterload and mitigate the risk of right heart failure. Conflicting evidence exists regarding the impact of these drugs on RV contractility. The aim of this study was to explore the acute effects of PDE5i on ventricular–vascular coupling and load-independent RV contractility. MethodsTwenty-two patients underwent right heart catheterization and gated equilibrium blood pool single photon emission computed tomography, before and after 20 mg intravenous sildenafil. Single photon emission computed tomography and right heart catheterization-derived data were used to calculate RV loading and contractility. ResultsPDE5i induced a decrease in the right atrial pressure (–43%), pulmonary artery (PA) mean pressure (–26%), and PA wedge pressure (PAWP; –23%), with favorable reductions in pulmonary vascular resistance (–41%) and PA elastance (–40%), and increased cardiac output (+13%) (all P < 0.01). The RV ejection fraction increased with sildenafil (+20%), with no change of RV contractility (P = 0.74), indicating that the improvement in the RV ejection fraction was related to enhanced RV–PA coupling (r = 0.59, P = 0.004) by a decrease in the ventricular load. RV diastolic compliance increased with sildenafil. The decrease in the PAWP correlated with RV end-diastolic volume decrease; no relationship was observed with the change in LV transmural pressure, suggesting decreased pericardial constraint. ConclusionsAcute PDE5i administration has profound RV afterload-reducing effects, improves the RVEF, decreases RV volumes, and decreases the PAWP, predominantly through relief of pericardial constraint, without effects on RV chamber contractility. These findings support further study of PDE5i in protection of RV function in advanced heart failure with reduced ejection fraction who are at risk of RV failure.

A closer look at physiological indicators of cardiovascular function post‐transplantation

A closer look at physiological indicators of cardiovascular function post‐transplantation

Variability in the Physiologic Response to Fluid Bolus in Pediatric Patients Following Cardiac Surgery.

Fluid boluses aiming to improve the cardiac output and oxygen delivery are commonly administered in children with shock. An increased mean arterial pressure in addition to resolution of tachycardia and improved peripheral perfusion are often monitored as clinical surrogates for improvement in cardiac output. The objective of our study is to describe changes in cardiac index, mean arterial pressure, and their relationship to other indices of cardiovascular performance. The objective of our study is to describe changes in cardiac index, mean arterial pressure, and their relationship to other indices of cardiovascular performance. We prospectively analyzed hemodynamic data from children in the cardiac ICU who received fluid bolus (10mL/kg of Ringers-Lactate over 30 min) for management of shock and/or hypoperfusion within 12h of cardiac surgery. Cardiac index responders and mean arterial pressure-responders were defined as CI ≥10% and mean arterial pressure ≥10%, respectively. We evaluated the gradient for venous-return (mean systemic filling pressure-central venous pressure), arterial load properties (systemic vascular resistance index and elastance index) and changes in vasopressor support after fluid bolus. Fifty-seven children between 1 month and 16 years (median Risk adjustment after congenital heart surgery Model for Outcome Surveillance in Australia and New Zealand score of 3.8 (interquartile range 3.7-4.6) received fluid bolus. Cardiac index-responsiveness and mean arterial pressure-responsiveness rates were 33% and 56%, respectively. No significant correlation was observed between changes in mean arterial pressure and cardiac index (r = 0.035, p = 0.79). Although the mean systemic filling pressure - central venous pressure and the number of cardiac index-responders after fluid bolus were similar, the arterial load parameters did not change in mean arterial pressure-nonresponders. Forty-three patients (75%) had a change in Vasoactive-Inotrope Score after the fluid bolus, of whom 60% received higher level of vasoactive support. The mean arterial pressure response to fluid bolus in cardiac ICU patients was unpredictable with a poor relationship between cardiac index-responsiveness and mean arterial pressure-responsiveness. Because arterial hypotension is frequently a trigger for administering fluids and changes in blood pressure are commonly used for tracking changes in cardiac output, we suggest a cautious and individualized approach to repeat fluid bolus based solely on lack of mean arterial pressure response to the initial fluid, since the implications include decreased arterial tone even if the cardiac index increases.

Pulmonary artery pulsatility index predicts prolonged inotrope/pulmonary vasodilator use after implantation of continuous flow left ventricular assist device.

Predictors of right ventricle (RV) dysfunction after continuous-flow left ventricular assist device (CF-LVAD) implantation in children are not well described. We explored the association of preimplantation Pulmonary Artery Pulsatility index (PAPi) and other hemodynamic parameters as predictors of prolonged postoperative inotropes/pulmonary vasodilator use after CF-LVAD implantation. Retrospective chart review. Single tertiary care pediatric referral center. Patients who underwent CF-LVAD implantation from January 2012 to October 2017. Preimplantation invasive hemodynamic parameters were analyzed to evaluate the association with post-CF-LVAD need for prolonged (>72hours) use of inotropes/pulmonary vasodilators. Preimplantation cardiac catheterization data was available for 12 of 44 patients who underwent CF-LVAD implant during the study period. Median (IQR) age and BSA of the cohort were 15.3 years (10.2, 18) and 1.74m2 (0.98, 2.03). Group 1 (n=6) included patients with need for prolonged inotropes/pulmonary vasodilator use after CF-LVAD implantation and Group 2 (n=6) included those without. Baseline demographic parameters, cardiopulmonary bypass time, and markers of RV afterload (pulmonary vascular resistance, PA compliance and elastance) were similar among the two groups. PAPi was significantly lower in group 1 compared to group 2 (0.96 vs 3.6, respectively; P=.004). Post-LVAD stay in the intensive care unit was longer for patients in group 1 (46 vs 23 days, P=.52). Brain natriuretic peptide was significantly higher at 3 months after implantation in group 1; P=.01. The need for inotropes/pulmonary vasodilators in the postoperative period can be predicted by the preimplantation intrinsic RV contractile reserve as assessed by PAPi rather than the markers of RV afterload. Further investigation and correlation with clinical outcomes is needed.

The Effects of Vasoconstriction And Volume Expansion on Veno-Arterial ECMO Flow.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is gaining widespread use in the treatment of severe cardiorespiratory failure. Blood volume expansion is commonly used to increase ECMO flow (QECMO), with risk of positive fluid balance and worsening prognosis. We studied the effects of vasoconstriction on recruitment of blood volume as an alternative for increasing QECMO, based on the concepts of venous return. In a closed chest, centrally cannulated porcine preparation (n = 9) in ventricular fibrillation and VA-ECMO with vented left atrium, mean systemic filling pressure (MSFP), and venous return driving pressure (VRdP) were determined in Euvolemia, during Vasoconstriction (norepinephrine 0.05, 0.125, and 0.2 μg/kg/min) and after Volume Expansion (3 boluses of 10 mL/kg Ringer's lactate). Maximum achievable QECMO was examined. Vasoconstriction and Volume Expansion both increased maximum achievable QECMO, delivery of oxygen (DO2), and MSFP, but right atrial pressure increased in parallel. VRdP did not change. The vascular elastance curve was shifted to the left by Vasoconstriction, with recruitment of stressed volume. It was shifted to the right by Volume Expansion with direct expansion of stressed volume. Volume Expansion decreased resistance to venous return and pump afterload. In a circulation completely dependent on ECMO support, maximum achievable flow directly depended on the vascular factors governing venous return-i.e., closing conditions, stressed vascular volume and the elastance and resistive properties of the vasculature. Both treatments increased maximum achievable ECMO flow at stable DO2, via increases in stressed volume by different mechanisms. Vascular resistance and pump afterload decreased with Volume Expansion.

Rolipram, a PDE4 Inhibitor, Enhances the Inotropic Effect of Rat Heart by Activating SERCA2a.

This study was designed to investigate the hemodynamic effect of rolipram, a phosphodiesterase type 4 (PDE4) inhibitor, in normal rat hearts both in vivo and in vitro and its underlying mechanism. The pressure-volume loop, isolated heart, and Ca2+ transients triggered by field stimulation or caffeine were used to analyze the hemodynamic mechanism of rolipram. The results demonstrated that rolipram (3 mg/kg, ip) significantly increased the in vivo rat heart contractility by enhancing stroke work, cardiac output, stroke volume, end-systolic volume, end-diastolic volume, end-systolic pressure, heart rate, ejection fraction, peak rate of rise of left pressure (+dp/dtmax), the slopes of end-systolic pressure-volume relationship (slope of ESPVR) named as left ventricular end-systolic elastance, and reduced the slopes of end-diastolic pressure-volume relationship (slope of EDPVR). Meanwhile, the systolic blood pressure, diastolic blood pressure, and pulse pressure were significantly enhanced by rolipram. Also, rolipram deviated normal ventricular-arterial coupling without changing the arterial elastance. Furthermore, rolipram (0.1, 1, 10 μM) also exerted positive inotropic effect in isolated rat hearts by increasing the left ventricular development pressure, and +dp/dtmax in non-paced and paced modes. Rolipram (10 μM) increased the SERCA2a activity, Ca2+ content, and Ca2+ leak rate without changing diastolic Ca2+ level. Rolipram had significant positive inotropic effect with less effect on peripheral vascular elastance and its underlying mechanism was mediated by increasing SERCA2a activity. PDE4 inhibition by rolipram resulted in a positive inotropic effect and might serve as a target for developing agents for the treatment of heart failure in clinical settings.

Vascular TSP1-CD47 signaling promotes sickle cell-associated arterial vasculopathy and pulmonary hypertension in mice.

Pulmonary hypertension (PH) is a leading cause of death in sickle cell disease (SCD) patients. Hemolysis and oxidative stress contribute to SCD-associated PH. We have reported that the protein thrombospondin-1 (TSP1) is elevated in the plasma of patients with SCD and, by interacting with its receptor CD47, limits vasodilation of distal pulmonary arteries ex vivo. We hypothesized that the TSP1-CD47 interaction may promote PH in SCD. We found that TSP1 and CD47 are upregulated in the lungs of Berkeley (BERK) sickling (Sickle) mice and patients with SCD-associated PH. We then generated chimeric animals by transplanting BERK bone marrow into C57BL/6J (n = 24) and CD47 knockout (CD47KO, n = 27) mice. Right ventricular (RV) pressure was lower in fully engrafted Sickle-to-CD47KO than Sickle-to-C57BL/6J chimeras, as shown by the reduced maximum RV pressure (P = 0.013) and mean pulmonary artery pressure (P = 0.020). The afterload of the sickle-to-CD47KO chimeras was also lower, as shown by the diminished pulmonary vascular resistance (P = 0.024) and RV effective arterial elastance (P = 0.052). On myography, aortic segments from Sickle-to-CD47KO chimeras showed improved relaxation to acetylcholine. We hypothesized that, in SCD, TSP1-CD47 signaling promotes PH, in part, by increasing reactive oxygen species (ROS) generation. In human pulmonary artery endothelial cells, treatment with TSP1 stimulated ROS generation, which was abrogated by CD47 blockade. Explanted lungs of CD47KO chimeras had less vascular congestion and a smaller oxidative footprint. Our results show that genetic absence of CD47 ameliorates SCD-associated PH, which may be due to decreased ROS levels. Modulation of TSP1-CD47 may provide a new molecular approach to the treatment of SCD-associated PH.

Haemodynamic profiles in adult Fontan patients: associated haemodynamics and prognosis.

The Fontan operation is associated with significant long-term morbidity and mortality, posing challenges in management. No haemodynamic classification has been established to aid management and prognostication of patients with Fontan palliation. Our aim was to assess haemodynamic profiles for Fontan patients and evaluate their relationships to prognosis. Eighty-four adult Fontan patients without obstruction or significant valve disease undergoing cardiac catheterization for Fontan-related co-morbidities were divided into four different haemodynamic profiles based on normal/high Fontan pressures (FP) (< 15 or ≥ 15 mmHg) and low/normal cardiac index (CI) (< 2.5 or ≥ 2.5 L/min/m2 ). Fourteen patients had low CI/high FP (17%), 24 low CI/normal FP (29%), 20 normal CI/high FP (24%), and 26 normal CI/normal FP (31%). Demographic and clinical data were similar among groups except for a trend towards a higher prevalence of cirrhosis in the normal CI/high FP (50%) group. Systemic vascular afterload, assessed by systemic vascular resistance and effective arterial elastance, was higher in patients with low CI/high FP and low CI/normal FP as compared to normal CI profiles. Pulmonary vascular resistance indices were higher in patients with low CI/high FP than all other profiles. The normal CI/high FP haemodynamic profile was an independent predictor of mortality (hazard ratio 4.1, 95% confidence interval 1.2-11.5). Heterotaxy and protein-losing enteropathy were also predictors of mortality on the multivariate model. The proposed haemodynamic classification provides prognostic information in adults post-Fontan with patients in the normal CI/high FP profile having worse survival. Whether this classification can guide management in these patients deserves further investigation.

Early Pulmonary Vascular Disease in Young Adults Born Preterm.

Rationale: Premature birth affects 10% of live births in the United States and is associated with alveolar simplification and altered pulmonary microvascular development. However, little is known about the long-term impact prematurity has on the pulmonary vasculature.Objectives: Determine the long-term effects of prematurity on right ventricular and pulmonary vascular hemodynamics.Methods: Preterm subjects (n = 11) were recruited from the Newborn Lung Project, a prospectively followed cohort at the University of Wisconsin-Madison, born preterm with very low birth weight (≤1,500 g; average gestational age, 28 wk) between 1988 and 1991. Control subjects (n = 10) from the same birth years were recruited from the general population. All subjects had no known adult cardiopulmonary disease. Right heart catheterization was performed to assess right ventricular and pulmonary vascular hemodynamics at rest and during hypoxic and exercise stress.Measurements and Main Results: Preterm subjects had higher mean pulmonary arterial pressures (mPAPs), with 27% (3 of 11) meeting criteria for borderline pulmonary hypertension (mPAP, 19-24 mm Hg) and 18% (2 of 11) meeting criteria for overt pulmonary hypertension (mPAP ≥ 25 mm Hg). Pulmonary vascular resistance and elastance were higher at rest and during exercise, suggesting a stiffer vascular bed. Preterm subjects were significantly less able to augment cardiac index or right ventricular stroke work during exercise. Among neonatal characteristics, total ventilatory support days was the strongest predictor of adult pulmonary pressure.Conclusions: Young adults born preterm demonstrate early pulmonary vascular disease, characterized by elevated pulmonary pressures, a stiffer pulmonary vascular bed, and right ventricular dysfunction, consistent with an increased risk of developing pulmonary hypertension.

Assessment of central hemodynamic effects of phenylephrine: an animal experiment.

Phenylephrine is an α1-adrenergic receptor agonist widely used to treat perioperative hypotension. Its other hemodynamic effects, in particular on preload and contractility, remain controversial. We, therefore, investigated the effect of continuously applied phenylephrine on central hemodynamics in eight mechanically ventilated domestic pigs. Mean arterial pressure (MAP) was increased in steps by 50%, and 100% using phenylephrine. Besides stroke volume (SV), cardiac output (CO), and MAP, mean systemic vascular resistance (SVR) and dynamic arterial elastance (Eadyn) were assessed for characterization of afterload. Changes in preload were assessed by central venous pressure (CVP), global end-diastolic volume (GEDV), mean systemic filling pressure analog (Pmsfa), pulse pressure variation (PPV), and stroke volume variation (SVV). Further, cardiac function index (CFI), global ejection fraction and dPmax were measured as markers of preload dependent contractility. MAP, SV, and CO significantly increased following both interventions, as did SVR. In contrast, Eadyn did not show significant changes. Although the volumetric preload variable GEDV increased after the first step of phenylephrine, this was not reflected by significant changes in CVP or Pmsfa. CFI and dPmax significantly increased after both steps. Phenylephrine does not only affect cardiac afterload, but also increases effective preload. In contrast to CVP and Pmsfa, this effect can be monitored by GEDV. Further, phenylephrine affects contractility.

Tissue-Resident TSP1-CD47 Signaling Promotes Sickle Cell-Associated Arterial Vasculopathy and Pulmonary Hypertension

Pulmonary hypertension (PH) is a chronic pulmonary complication of sickle cell disease (SCD) and a leading cause of death in adults. The exact molecular causes of SCD-associated PH are unknown although pathologic hemolysis related to chronic nitric oxide depletion and oxidative stress are recognized as contributing factors. We have reported that the protein thrombospondin-1 (TSP1) is elevated in the plasma of patients with SCD and by interacting with its receptor CD47 limits vasodilation of distal pulmonary arteries ex vivo . We hypothesized that the TSP1-CD47 interaction may promote PH in the BERK sickle mouse model. To test this hypothesis, we inquired whether TSP1 and CD47 are upregulated in the lungs of BERK mice and patients with SCD-associated PH. We found that lungs of age matched male 13-14 months old BERK sickle mice overexpressed TSP1 and CD47 as compared to both C57BL/6J and Hemi BERK mice and also confirmed our prior findings that sickle mice develop PH as they age. Immunohistochemistry of lung sections from 6 patients with SCD-associated PH revealed increased levels of CD47 as compared to sections from patients without PH or overt lung disease. We interrogated the TSP1-CD47 axis in vivo by generating chimeric animals with a sickle erythropoiesis on a CD47KO background by transplanting BERK sickle bone marrow into C57BL/6J (n=24) and CD47 knockout (CD47KO, n=27) mice. Fully engrafted chimeric mice underwent pulmonary hemodynamic assessment after 6 months. Right ventricular (RV) pressures were lower in Sickle-to-CD47KO chimeras as compared to Sickle-to-C57BL/6J chimeras as shown by the reduced maximum pressure of the RV (22.1 ± 3.6 vs. 28.1 ± 8.8 mmHg, p=0.013) and mean pulmonary artery pressure (15.3 ± 2.6 vs. 18.8 ± 5.7 mmHg, p=0.020). The afterload of the Sickle-to-CD47KO chimeras was lower compared to Sickle-to-C57BL/6J chimeras as shown by the diminished pulmonary vascular resistance (1.2 ± 0.7 vs. 2.4 ± 2.2 Wood units, p=0.024) and RV effective arterial elastance (1.5 ± 0.9 vs. 2.7 ± 2.6 mmHg/µL, p=0.052). The RV diastolic function as measured by the RV dP/dtmin also showed a trend towards improvement as compared to Sickle-to-C57BL/6J chimeras (-1297.0 ± 318.2 vs. -1604.0 ± 668.2 mmHg/s, p=0.059). Finally, the Sickle-to-CD47KO chimeras had a tendency for less RV hypertrophy as evidenced by lower RV free wall weight as compared to Sickle-to-C57BL/6J chimeras (21.45 ± 5.0 vs. 24.63 ± 6.0 mg, p=0.056). Interestingly, plasma levels of soluble TSP1 were reduced in Sickle-to-CD47KO chimeras (61.45 ± 10.11 vs. 76.89 ± 10.84 pg/mL, p=0.012). On myography, aortic segments from Sickle-to-CD47KO chimeras had improved relaxation to the endothelial activator acetylcholine. We hypothesized that in SCD TSP1-CD47 signaling promotes PH, in part, by increasing ROS generation. Treatment with exogenous TSP1 (2.2x10-9 M, a concentration found in the plasma of SCD patients) stimulated increased levels of superoxide and hydrogen peroxide in human pulmonary artery endothelial cells by cytochrome C and Amplex Red assays, respectively. Furthermore, lungs of CD47KO chimeras had decreased oxidative damage as measured by reduced 4-hydroxynonenal and 3-nitrotyrosine staining vs. Sickle-to-C57BL/6J chimeras. Finally, suppression of CD47 with a morpholino (10 mg/kg body weight i.p. weekly) for 8 weeks (n=8 animals) also reduced pulmonary pressures in BERK mice. Our results show that genetic deletion or suppression of CD47 ameliorates SCD-associated PH, which may be due, in part, to decreased ROS levels. Targeting TSP1-CD47 may provide a new molecular approach to the treatment of SCD-associated PH. DisclosuresIsenberg:Tioma Therapeutics: Equity Ownership; Radiation Control Technologies, Inc.: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

Real Time 3D echocardiography (RT3D) for assessment of ventricular and vascular function in hypertensive and heart failure patients

BackgroundCardiac and systemic hemodynamics have been historically in the domain of invasive cardiology, but recent advances in real-time 3-Dimensional echocardiography (RT3D echo) provide a reliable measurement of ventricular volumes, allowing to measure a set of hemodynamic parameters previously difficult or impossible to obtain with standard 2D echo.AimTo assess the feasibility of a comprehensive hemodynamic study with RT-3D echo.MethodsWe enrolled 136 patients referred for routine echocardiography: 44 normal (N), 57 hypertensive (HYP), and 35 systolic heart failure patients (HF). All patients underwent standard 2D echo examination followed by RT3D echo examination, including measurement of left ventricular (LV) end-diastolic and end-systolic volumes and derived assessment of LV elastance (an index of LV contractility), arterial elastance (characterizing the distal impedance of the arterial system downstream of the aortic valve); ventricular-arterial coupling (a central determinant of net cardiovascular performance); systemic vascular resistances. Blood pressure was derived from cuff sphygmomanometer and heart rate from ECG.ResultsA complete 2D echo was performed in all 136 patients. 3D echo examination was obtained in 130 patients (feasibility = 95 %). Standard 2D echo examination was completed in 14.8 ± 2.2 min. Acquisition of 3D images required an average time of 5 ± 0.9 min (range 3.5-7.5 min) and image analysis was completed in 10.1 ± 2.8 min (range 6–12 min) per patient. Compared to N and HYP, HF patients showed reduced LV elastance (1.7 ± 1.5 mmHg mL-1 m-2, p <0.001 vs N = 3.8 ± 1.3 and HYP = 3.8 ± 1.3) and ventricular-arterial coupling (0.6 ± 0.5, p < 0.01 vs N = 1.4 ± 0.4 and HYP = 1.2 ± 0.4). Systemic vascular resistances were highest in HYP (2736 ± 720, p < .01 vs N = 1980 ± 432 and vs HF = 1855 ± 636 dyne*s/cm5). The LV elastance was related to EF (r = 0.73, p < 0.01) and arterial pressure was moderately related to vascular elastance (r = 0.54, p < 0.01). The ventricular-arterial coupling was unrelated to systemic vascular resistances (r = −0.04, p NS).ConclusionRT-3D echo allows a non invasive, comprehensive assessment of cardiac and systemic hemodynamics, offering insight access to key variables – such as increased systemic vascular resistances in hypertensives and reduced ventricular-arterial coupling in heart failure patients.

Augmentation Index Immediately after Maximal Exercise in Patients with Type 2 Diabetes Mellitus

Patients with type 2 diabetes mellitus (T2DM) have exaggerated brachial and central (ascending aortic) blood pressure (BP) during exercise, which is associated with adverse outcomes. Central systolic loading, represented by the augmentation index (AIx), may contribute to exaggerated exercise central BP. This study sought to compare the central AIx response to peak exercise in T2DM and control patients and to identify mechanisms of altered exercise central AIx. Central BP and AIx were quantified by radial tonometry at rest and immediately after peak treadmill exercise in 106 patients with T2DM and 106 nondiabetic controls, pair-matched by age, gender, peak exercise brachial BP, and postexercise HR corresponding to tonometry acquisition. Cardiac volumes (by echocardiography) were assessed in a subgroup (22 T2DM and 22 controls) to derive rest and postexercise arterial-ventricular coupling parameters, including cardiac index (stroke volume index × HR), peripheral vascular resistance index (cardiac index / mean BP), and effective arterial elastance index (end-systolic pressure / stroke volume index). Reserve parameters (exercise--rest) were also defined. Patients with T2DM had lower postexercise central AIx (-1% ± 13% vs 3% ± 14%, P = 0.038) and greater central AIx reserve (-24% ± 13% vs -20% ± 11%, P = 0.002) compared with controls, despite raised postexercise peripheral vascular resistance index (P = 0.013) and effective arterial elastance index (P = 0.011); these parameters independently predicted higher central AIx at rest (P < 0.01) but not after exercise. Moreover, T2DM was independently associated with lower postexercise central AIx (β = -0.21, P = 0.006). Cardiac index reserve, which was blunted in T2DM (P = 0.004), represented the only independent correlate of central AIx reserve (r = 0.39, P = 0.01). Patients with T2DM have significantly (and paradoxically) lower postexercise central AIx and greater central AIx reserve, which may be explained by an impaired cardiac functional reserve.

Preliminary study on ventricular arterial coupling of patients with hypertension by ultrasonography

BackgroundAgeing and chronic diseases, such as hypertension and diabetes, modify the structure and function of both the arteries and ventricles. The ventricular performance is influenced by arterial load and affects...

Pulmonary Arterial Elastance for Estimating Right Ventricular Afterload in Systolic Heart Failure

Assessment of right ventricular afterload in systolic heart failure seems mandatory as it plays an important role in predicting outcome. The purpose of this study is to estimate pulmonary vascular elastance as a reliable surrogate for right ventricular afterload in systolic heart failure. Forty-two patients with systolic heart failure (ejection fraction <35%) were studied by right heart catheterization. Pulmonary arterial elastance was calculated with three methods: Ea(PV) = (end-systolic pulmonary arterial pressure)/stroke volume; Ea*(PV) = (mean pulmonary arterial pressure - pulmonary capillary wedge pressure)/stroke volume; and PPSV = pulmonary arterial pulse pressure (systolic - diastolic)/stroke volume. These measures were compared with pulmonary vascular resistance ([mean pulmonary arterial pressure - pulmonary capillary wedge pressure]/CO). All estimates of pulmonary vascular elastance were significantly correlated with pulmonary vascular resistance (r=0.772, 0.569, and 0.935 for Ea(PV), Ea*(PV), and PPSV, respectively; P <.001). Pulmonary vascular elastance can easily be estimated by routine right heart catheterization in systolic heart failure and seems promising in assessment of right ventricular afterload.

Epigenetics and Hypertension

Epigenetics refers to mechanisms for environment-gene interactions (mainly by methylation of DNA and modification of histones) that do not alter the underlying base sequence of the gene. This article reviews evidence for epigenetic contributions to hypertension. For example, DNA methylation at CpG islands and histone acetylation pathways are known to limit nephron development, thereby unmasking hypertension associated with exposure to a high-salt diet. Maternal water deprivation and protein deficiency are shown to increase expression of renin-angiotensin system genes in the offspring. The methylation pattern of a serine protease inhibitor gene in human placentas is shown to be a marker for preeclampsia-associated hypertension. Mental stress induces phenylethanolamine n-methyltransferase, which may act as a DNA methylase and mimic the gene-silencing effects of methyl CpG binding protein-2 on the norepinephrine transporter gene, which, in turn, may exaggerate autonomic responsiveness. A disrupter of telomeric silencing (Dot1) is known to modulate the expression of a connective-tissue growth-factor gene associated with blood vessel remodeling, which could alter vascular compliance and elastance. Dot1a also interacts with the Af9 gene to produce high sodium channel permeability and silences the hydroxysteroid dehydrogenase-11β2 gene, thereby preventing metabolism of cortisol to cortisone and overstimulating aldosterone receptors. These findings indicate targets for environment-gene interactions in various hypertensive states and in essential hypertension.

Homocysteine to Hydrogen Sulfide or Hypertension

Hyperhomocysteinemia, an increased level of plasma homocysteine, is an independent risk factor for the development of premature arterial fibrosis with peripheral and cerebro-vascular, neurogenic and hypertensive heart disease, coronary occlusion and myocardial infarction, as well as venous thromboembolism. It is reported that hyperhomocysteinemia causes vascular dysfunction by two major routes: (1) increasing blood pressure and, (2) impairing the vasorelaxation activity of endothelial-derived nitric oxide. The homocysteine activates metalloproteinases and induces collagen synthesis and causes imbalances of elastin/collagen ratio which compromise vascular elastance. The metabolites from hyperhomocysteinemic endothelium could modify components of the underlying muscle cells, leading to vascular dysfunction and hypertension. Homocysteine metabolizes in the body to produce H(2)S, which is a strong antioxidant and vasorelaxation factor. At an elevated level, homocysteine inactivates proteins by homocysteinylation including its endogenous metabolizing enzyme, cystathionine gamma-lyase. Thus, reduced production of H(2)S during hyperhomocysteinemia exemplifies hypertension and vascular diseases. In light of the present information, this review focuses on the mechanism of hyperhomocysteinemia-associated hypertension and highlights the novel modulatory role of H(2)S to ameliorate hypertension.

131 Preload, contractility and afterload during the course of normal pregnancy – an echocardiographic study

Purpose Pregnancy is a physiologic condition associated with increased intravascular volume and decreased systemic vascular resistance. The aim of the study was to provide a longitudinally evaluation of the normal maternal cardiac function through echocardiography. Methods Twenty-seven pregnant women (mean age 30.7±2.9y) and 14 age and sex-matched non-pregnant controls (30.2±4.4y) were included. Echocardiography with conventional and speckle tracking based myocardial deformation imaging were performed longitudinally at 11-14, 22-24 and 32 weeks during pregnancy, and at inclusion for the control group. Total vascular resistance (TVR), aortic distensibility (ADis) and arterial elastance (Ea) were calculated for characterization of vascular adaptation. Beside conventional echocardiographic parameters, LV end-systolic wall stress (ESWS) and end-systolic elastance (Ees) were calculated, and ventriculo-arterial coupling index was derived. Results During pregnancy we found a progressive increase in LVEDV (93.8 ± 7.0 vs 88.8 ± 6.0 ml in 3 rd vs 1 st trimester, p rd trimester and lower values than in control during the whole pregnancy, while ADis progressively increased reaching the peak during the 3 rd trimester (7.55 ± 2.5 vs 6.25 ± 2.1 mmHg-1, p Conclusions Pregnancy is associated with increased preload and decreased afterload, with progressively decreased total vascular resistance and increased aortic compliance, decreased end-systolic wall stress, increased cardiac output and preserved ventriculo-arterial coupling.