Influence of right ventricular pressure and volume overload on right and left ventricular diastolic function.

Ventricular interdependence may account for altered ventricular mechanics in congenital heart disease. The present study aimed to identify differences in load-dependent right ventricular (RV)-left ventricular (LV) interactions in porcine models of pulmonary stenosis (PS) and pulmonary insufficiency (PI) by invasive admittance-derived hemodynamics in conjunction with noninvasive cardiovascular magnetic resonance (CMR). Seventeen pigs were used in the study (7 with PS, 7 with PI, and 3 controls). Progressive PS was created by tightening a Teflon tape around the pulmonary artery, and PI was created by excising 2 leaflets of the pulmonary valve. Admittance catheterization data were obtained for the RV and LV at 10 to 12 weeks after model creation, with the animal ventilated under temporary diaphragm paralysis. CMR was performed in all animals immediately prior to pressure-volume catheterization. In the PS group, RV contractility was increased, manifested by increased end-systolic elastance (mean difference, 1.29 mm Hg/mL; 95% confidence interval [CI], 0.57-2.00 mm Hg/mL). However, in the PI group, no significant changes were observed in RV systolic function despite significant changes in RV diastolic function. In the PS group, LV end-systolic volume was significantly lower compared with controls (mean difference, 25.1 mL; 95% CI, -40.5 to -90.7 mL), whereas in the PI group, the LV showed diastolic dysfunction, demonstrated by an elevated isovolumic relaxation constant and ventricular stiffness (mean difference, 0.03 mL-1; 95% CI, -0.02 to 0.09 mL-1). The LV exhibits systolic dysfunction and noncompliance with PI. PS is associated with preserved LV systolic function and evidence of some LV diastolic dysfunction. Interventricular interactions influence LV filling and likely account for differential effects of RV pressure and volume overload on LV function.

Jani V ，Konecny F ，Shelby A ，Kulkarni A ，Hammel J ，Schuster A ，Lof J ，Right Heart Research Group ，Danford D ，Kutty S ... -  《-》

Adverse ventricular-ventricular interactions in right ventricular pressure load: Insights from pediatric pulmonary hypertension versus pulmonary stenosis.

Right ventricular (RV) pressure overload has a vastly different clinical course in children with idiopathic pulmonary arterial hypertension (iPAH) than in children with pulmonary stenosis (PS). While RV function is well recognized as a key prognostic factor in iPAH, adverse ventricular-ventricular interactions and LV dysfunction are less well characterized and the pathophysiology is incompletely understood. We compared ventricular-ventricular interactions as hypothesized drivers of biventricular dysfunction in pediatric iPAH versus PS Eighteen iPAH, 16 PS patients and 18 age- and size-matched controls were retrospectively studied. Cardiac cycle events were measured by M-mode and Doppler echocardiography. Measurements were compared between groups using ANOVA with post hoc Dunnet's or ANCOVA including RV systolic pressure (RVSP; iPAH 96.8 ± 25.4 mmHg vs. PS 75.4 ± 18.9 mmHg; P = 0.011) as a covariate. RV-free wall thickening was prolonged in iPAH versus PS, extending beyond pulmonary valve closure (638 ± 76 msec vs. 562 ± 76 msec vs. 473 ± 59 msec controls). LV and RV isovolumetric relaxation were prolonged in iPAH (P < 0.001; LV 102.8 ± 24.1 msec vs. 63.1 ± 13.7 msec; RV 95 [61-165] vs. 28 [0-43]), associated with adverse septal kinetics; characterized by rightward displacement in early systole and leftward displacement in late RV systole (i.e., early LV diastole). Early LV diastolic filling was decreased in iPAH (73 ± 15.9 vs. PS 87.4 ± 14.4 vs. controls 95.8 ± 12.5 cm/sec; P = 0.004). Prolonged RVFW thickening, prolonged RVFW isovolumetric times, and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in pediatric iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency in iPAH and may form the basis for worse clinical outcomes. We used clinically derived data to study the pathophysiology of ventricular-ventricular interactions in right ventricular pressure overload, demonstrating distinct differences between pediatric pulmonary arterial hypertension (iPAH) and pulmonary stenosis (PS). Altered timing of right ventricular free wall contraction and profound septal dyskinesia are associated with interventricular mechanical discoordination and decreased early LV filling in iPAH much more than PS These adverse mechanics affect systolic and diastolic biventricular efficiency, independent of right ventricular systolic pressure.

Driessen MM ，Hui W ，Bijnens BH ，Dragulescu A ，Mertens L ，Meijboom FJ ，Friedberg MK ... -  《Physiological Reports》

Maintained right ventricular pressure overload induces ventricular-arterial decoupling in mice.

What is the central question of this study? The aim was to investigate whether complementary assessment of non-invasive ultrasound imaging together with closed chest-derived intracardiac pressure-volume catheterization is applicable to mice for an in-depth characterization of right ventricular (RV) function even upon maintained pressure overload. What is the main finding and its importance? Characterization of RV function by the complementary use of echocardiographic imaging together with pressure-volume catheterization reveals ventricular-arterial decoupling upon maintained pressure overload, where RV systolic function correlates with ventricular-arterial coupling rather than contractility, whereas diastolic function correlates well with RV diastolic pressure. This combined approach allows us to phenotype RV function and dysfunction better in genetically modified and/or pharmacologically treated mice. Assessment of right ventricular (RV) function in rodents is a challenge because of the complex RV anatomy and structure. To date, the best characterization of RV function has been achieved by accurate cardiovascular phenotyping, involving a combination of non-invasive imaging and intracardiac pressure-volume measurements. We sought to investigate the feasibility of two complementary phenotyping techniques for the evaluation of RV function in an experimental mouse model of sustained RV pressure overload. Mice underwent either sham surgery (n = 5) or pulmonary artery banding (n = 8) to induce isolated RV pressure overload. After 3 weeks, indices of RV function were assessed by echocardiography (Vevo2100) and closed chest-derived invasive pressure-volume measurements (PVR-1030). Pulmonary artery banding resulted in RV hypertrophy and dilatation accompanied by systolic and diastolic dysfunction. Invasive RV haemodynamic measurements demonstrated an increased end-systolic elastance and arterial elastance after pulmonary artery banding compared with sham operation, resulting in ventricular-arterial decoupling. Regression analysis revealed that tricuspid annular plane systolic excursion is correlated with ventricular-arterial coupling (r² = 0.77, P = 0.002) rather than with RV contractility (r² = -0.61, P = 0.07). Furthermore, the isovolumic relaxation time to ECG-derived R-R interval and the ratio of the early diastolic peak velocity measured by pulsed wave Doppler to the early diastolic peak obtained during tissue Doppler imaging correlate well with RV end-diastolic pressure (r² = 0.87, P = 0.0001 and r² = 0.82, P = 0.0009, respectively). Commonly used indices of systolic RV function are associated with RV-arterial coupling rather than contractility, whereas diastolic indices well correlate with end-diastolic pressure when there is maintained pressure overload.

Boehm M ，Lawrie A ，Wilhelm J ，Ghofrani HA ，Grimminger F ，Weissmann N ，Seeger W ，Schermuly RT ，Kojonazarov B ... -  《-》

Long-term importance of right ventricular outflow tract patch function in patients with pulmonary regurgitation.

Chronic pulmonary regurgitation (PR) has deleterious effects on right ventricular (RV) function in repaired tetralogy of Fallot (ToF). However, there are little data regarding right ventricular outflow tract (RVOT) contractile dysfunction in response to chronic PR and on both RV and LV volumes and function. We retrospectively identified consecutive patients with PR who were referred for magnetic resonance imaging quantification of "free PR" detected on echocardiography between 2003 and 2008. Patients had ToF and a transannular patch procedure (n = 30, 25.1 ± 1.2 years) or PR resulting from valvar pulmonary stenosis treated with surgical or percutaneous valvotomy (n = 30, 26.6 ± 1.8 years). The ToF and the PS groups were well matched for age at scan, age at repair surgery in ToF or initial valvotomy in PS, duration of exposure to PR, body surface area, heart rate, PR fraction, net forward pulmonary artery flow, and main and branch pulmonary artery dimensions. Severe PR fractions were identified in both groups (ToF: 40% ± 1% vs PS: 37% ± 2%, P = .2). Indexed RV and LV end-diastolic volumes were similar for both ToF and PS groups (RV end-diastolic volume index: 137 ± 6 mL/m(2) vs 128 ± 5 mL/m(2), P = .2, and LV end-diastolic volume index: 72 ± 2 mL/m(2) vs 67 ± 2 mL/m(2), P = .1, respectively). RV mass was also similar between groups (95 ± 5 g vs 81 ± 6 g, respectively, P = .08). However, indexed RV and LV end-systolic volumes were consistently higher in ToF when compared with PS (RV end-systolic volume index: 70 ± 5 mL/m(2) vs 54 ± 3 mL/m(2), P < .01, and LV end-systolic volume index: 29 ± 1 mL/m(2) vs 22 ± 1 mL/m(2), P < .01, respectively). These changes were reflected in lower biventricular systolic function in patients with ToF when compared with PS (RV ejection fraction: 52% ± 1.5% vs 59% ± 1%, P < .001, and LV ejection fraction: 61% ± 1% vs 67 ± 1%, P < .001, respectively). Although RV transannular plane systolic excursion was not significantly different between the groups (P = .86), the RV outflow tract was considered contractile in only 50% of patients with ToF compared with 93% of patients with PS (P = .0004). RV volumes and function were similar when only patients with contractile RV outflow tracts were compared. RV outflow tract patch dysfunction in repaired ToF is responsible for higher end-systolic volumes and thus lower global measures of ventricular systolic function. These findings were not evident in cases of PS treated with valvotomy with comparable amount of PR. These observations highlight the importance of the initial repair surgery in ToF for late outcomes.

Puranik R ，Tsang V ，Lurz P ，Muthurangu V ，Offen S ，Frigiola A ，Norman W ，Walker F ，Bonhoeffer P ，Taylor AM ... -  《-》

Dynamic right and left ventricular interactions in the pig.

What is the central question of this study? Are the mechanisms that cause ventricular interdependence different when due to primary right to left ventricular pressure loading? What is the main finding and its importance? An instantaneous selective increase in aortic pressure causes an immediate increase in right ventricular end-systolic pressure independent of the pericardium, whereas a selective increase in pulmonary artery pressure decreases left ventricular diastolic compliance owing to a subsequent increasing right ventricular end-diastolic volume as a function of an intact pericardium limiting biventricular volume. Changes in contraction synchrony of either ventricle do not appear to be causing these effects. I characterized the dynamic factors determining ventricular interdependence with and without the pericardium. I measured right (RV) and left ventricular (LV) pressures and volumes simultaneously using conductance catheters in seven pentobarbitone-anaesthetized open-chested 5- to 7-week-old piglets. I studied these effects during apnoea, inferior vena caval occlusion and rapid partial aortic and pulmonary arterial occlusions. Conductance catheter-defined long-axis regional volumes were assessed to define regional contractile synchrony. Closed-pericardium measures were made from an initial (baseline) volume, then after two 20 ml kg-1 fluid loads followed by an open-pericardium step. Baseline RV and LV volumes were similar. Aortic occlusion increased LV pressures and volumes and RV end-systolic pressure such that RV end-systolic elastance increased without changes in RV contraction synchrony, not affected by the pericardium. Pulmonary artery occlusion increased RV end-systolic pressure but not end-systolic volume. On the subsequent beat, RV end-diastolic pressure increased, whereas LV end-diastolic volume and diastolic compliance decreased. These effects were attenuated by opening the pericardium. Contraction synchrony across longitudinal segments was unaltered by either aortic or pulmonary artery occlusion. I conclude that the determinants of systolic and diastolic ventricular interdependence are different. Increasing RV pressures causes diastolic RV-to-LV interdependence, decreasing LV diastolic compliance and dependent on an intact pericardium. An increase in LV end-systolic pressure increases RV end-systolic elastance independent of the pericardium and has a minimal effect on RV diastolic function or contraction synchrony.

Pinsky MR 《-》