Diastolic Ventricular Interaction Research Articles

Frequency of RV Diastolic Dysfunction in Chronic Heart Failure Patients

Objectives: In this cross-sectional study we aim to assess the frequency of RVDD in chronic heart failure patients with reduced EF who visited as outpatient in a tertiary care hospital.
 Methodology: We included consecutive patients with chronic heart failure who had reduced EF. We assessed these patients for RVDD if they had normal RV systolic function and pulmonary artery pressures. The RVDD was categorized as normal, impaired relaxation, pseudonormal filling and restricted filling according to ASE guideline. RVDD grades were compared with LV systolic dysfunction and diastolic dysfunction grades.
 Results: Out of 199 patients evaluated, 66.3% (132) were male will with the mean age of 56.8 ± 12 years. The majority, 176, 88.4% of patients were with diagnosis if ICMP. The RVDD was noted in 112 (56.3%) patients out of which 30 (26.8%) had stage 1 (impaired relaxation) 78 (69.6%) had stage 2 (pseudonormal) and 4 (3.6%) patients had grade 3 (restrictive filling) RVDD. When compared a statistically significant association (P < 0.001) was observed between LV and RV diastolic dysfunction.
 Conclusion: RVDD is under diagnosed entity of neglected ventricle which is significantly associated with LV systolic and diastolic dysfunction even if the RV systolic function is normal. The prognostic significance of this diastolic ventricular interaction needs to be further investigated.

Significance of echocardiographic right ventricular predictors of adverse prognosis in right ventricular dysfunction in patients with HFrEF

Abstract Funding Acknowledgements Type of funding sources: None. Background Dysfunction of the RV in patients with HFrEF is a prognostically unfavorable factor, which depends on the etiology, the duration of myocardial damage and the tactics of the treatment (Pharmacotherapy, Heart Surgery, CRTD, Heart Transplantation). RV function in patients with HFrEF realized in the concept of continuous contraction of the muscle tape proposed by Torrent-Guasp, where systolic and diastolic interventricular interactions are carried out through the common IVS and implemented in the degree of dyssynchrony of ventricular contraction. 3DERV and STE (GLSRV, FWLS) may add the prognostic value of the more commonly used RV functional parameters as the sensitive echocardiographic predictors of worse prognosis in patients with HFrEF. Methods and Results A total of 79 patients with HFrEF (age, from 26 to 77 years; the clinical manifestations of HFrEF corresponded to NYHA III in 52 patients (71%), NYHA IV in 27 patients (29%); LV EF ≤ 35%). The etiology of HFrEF was mainly connected to patients with ischemic heart disease- 50 (63.2%), non-ischemic genesis 29 (36, 7%).The primary endpoint was a death in the follow-up period of up to 3 years in 33 patients (45,2%). An adverse outcomes and mortality during the first year was 17 (23,2%). All patients were divided into subgroups 1 (n = 40) - survived during the 3-year, subgroups 2 (n = 33) - died during the 3-year follow-up period. The presence of RV dysfunction in patients with HFrEF was independently associated with concomitant LV dysfunction but not with PASP (PASP/GLSLV, % (р=0,94), PASP/FWLS RV, % (р=0,97). RV contractility was realized through systolic and diastolic ventricular interactions, mediated through the shared IVS. This putative mechanism was supported by the independent association between septal S’ and S (HR - 1,12; 95%; Cl 0,99-1,26; p = 0,049), GLS BS LV, % и FWLS BS RV, % (HR - 0,90; 95%; Cl 0,79-1,00; p = 0,040). Kaplan–Meier plot, RVFWS > -15%, (χ2 – 4,438; р < 0,035), GLS >-10%, (χ2 – 3,796; р< 0,05), RVBSLS >-15%, (χ2 – 11,986; р = 0,0005), 3DERVEF <25% (χ2 – 7,518; р = 0,006), %CVCI <30% (χ2 – 7,85; р = 0,005), 3DE RAV > 100 ml (χ2 – 4,36; р = 0,036) were an independent predictors of worse prognosis in patients with HFrHF. The curves of the ROC analysis demonstrated a sensitivity of GLSRV - 80.7% as a prognostic factor of survival in patients with HrEF. At the same time, FWLS RV had a specificity (87.5%) compared to GLSRV, %, the longitudinal deformation of the isolated segments of the FWRV, FAC, %VCI collapse, ESDA/SA of RV, RAV. Conclusions RV systolic dysfunction is a strong and independent predictor of in HFrEF. In case of HFrEF the longitudinal mechanism of RV reduction is more sensitive than others. GLSRV, FWS RV, 3DRVEF, %VCI collapse has been proposed as a more accurate and sensitive tool to evaluate RV function in longitudinal displacement of patients with HFrEF. Abstract Figure. Kaplan–Meier plot GLS, 3DEEFRV, FWLS Abstract Figure. ROC analysis

Treatment of right ventricular dysfunction and heart failure in pulmonary arterial hypertension.

Right heart dysfunction and failure is the principal determinant of adverse outcomes in patients with pulmonary arterial hypertension (PAH). In addition to right ventricular (RV) dysfunction, systemic congestion, increased afterload and impaired myocardial contractility play an important role in the pathophysiology of RV failure. The behavior of the RV in response to the hemodynamic overload is primarily modulated by the ventricular interaction and its coupling to the pulmonary circulation. The presentation can be acute with hemodynamic instability and shock or chronic producing symptoms of systemic venous congestion and low cardiac output. The prognostic factors associated with poor outcomes in hospitalized patients include systemic hypotension, hyponatremia, severe tricuspid insufficiency, inotropic support use and the presence of pericardial effusion. Effective therapeutic management strategies involve identification and effective treatment of the triggering factors, improving cardiopulmonary hemodynamics by optimization of volume to improve diastolic ventricular interactions, improving contractility by use of inotropes, and reducing afterload by use of drugs targeting pulmonary circulation. The medical therapies approved for PAH act primarily on the pulmonary vasculature with secondary effects on the right ventricle. Mechanical circulatory support as a bridge to transplantation has also gained traction in medically refractory cases. The current review was undertaken to summarize recent insights into the evaluation and treatment of RV dysfunction and failure attributable to PAH.

Diastolic Ventricular Interaction in Heart Failure With Preserved Ejection Fraction.

BackgroundExercise‐induced pulmonary hypertension is common in heart failure with preserved ejection fraction (HFpEF). We hypothesized that this could result in pericardial constraint and diastolic ventricular interaction in some patients during exercise.Methods and ResultsContrast stress echocardiography was performed in 30 HFpEF patients, 17 hypertensive controls, and 17 normotensive controls (healthy). Cardiac volumes, and normalized radius of curvature (NRC) of the interventricular septum at end‐diastole and end‐systole, were measured at rest and peak‐exercise, and compared between the groups. The septum was circular at rest in all 3 groups at end‐diastole. At peak‐exercise, end‐systolic NRC increased to 1.47±0.05 (P<0.001) in HFpEF patients, confirming development of pulmonary hypertension. End‐diastolic NRC also increased to 1.54±0.07 (P<0.001) in HFpEF patients, indicating septal flattening, and this correlated significantly with end‐systolic NRC (ρ=0.51, P=0.007). In hypertensive controls and healthy controls, peak‐exercise end‐systolic NRC increased, but this was significantly less than observed in HFpEF patients (HFpEF, P=0.02 versus hypertensive controls; P<0.001 versus healthy). There were also small, non‐significant increases in end‐diastolic NRC in both groups (hypertensive controls, +0.17±0.05, P=0.38; healthy, +0.06±0.03, P=0.93). In HFpEF patients, peak‐exercise end‐diastolic NRC also negatively correlated (r=−0.40, P<0.05) with the change in left ventricular end‐diastolic volume with exercise (ie, the Frank‐Starling mechanism), and a trend was noted towards a negative correlation with change in stroke volume (r=−0.36, P=0.08).ConclusionsExercise pulmonary hypertension causes substantial diastolic ventricular interaction on exercise in some patients with HFpEF, and this restriction to left ventricular filling by the right ventricle exacerbates the pre‐existing impaired Frank‐Starling response in these patients.

The overloaded right heart and ventricular interdependence.

The right and the left ventricle are interdependent as both structures are nested within the pericardium, have the septum in common and are encircled with common myocardial fibres. Therefore, right ventricular volume or pressure overloading affects left ventricular function, and this in turn may affect the right ventricle. In normal subjects at rest, right ventricular function has negligible interaction with left ventricular function. However, the right ventricle contributes significantly to the normal cardiac output response to exercise. In patients with right ventricular volume overload without pulmonary hypertension, left ventricular diastolic compliance is decreased and ejection fraction depressed but without intrinsic alteration in contractility. In patients with right ventricular pressure overload, left ventricular compliance is decreased with initial preservation of left ventricular ejection fraction, but with eventual left ventricular atrophic remodelling and altered systolic function. Breathing affects ventricular interdependence, in healthy subjects during exercise and in patients with lung diseases and altered respiratory system mechanics. Inspiration increases right ventricular volumes and decreases left ventricular volumes. Expiration decreases both right and left ventricular volumes. The presence of an intact pericardium enhances ventricular diastolic interdependence but has negligible effect on ventricular systolic interdependence. On the other hand, systolic interdependence is enhanced by a stiff right ventricular free wall, and decreased by a stiff septum. Recent imaging studies have shown that both diastolic and systolic ventricular interactions are negatively affected by right ventricular regional inhomogeneity and prolongation of contraction, which occur along with an increase in pulmonary artery pressure. The clinical relevance of these observations is being explored.

Short-term intravenous sodium nitrite infusion improves cardiac and pulmonary hemodynamics in heart failure patients.

Background—Nitrite exhibits hypoxia-dependent vasodilator properties, selectively dilating capacitance vessels in healthy subjects. Unlike organic nitrates, it seems not to be subject to the development of tolerance. Currently, therapeutic options for decompensated heart failure (HF) are limited. We hypothesized that by preferentially dilating systemic capacitance and pulmonary resistance vessels although only marginally dilating resistance vessels, sodium nitrite (NaNO2) infusion would increase cardiac output but reduce systemic arterial blood pressure only modestly. We therefore undertook a first-in-human HF proof of concept/safety study, evaluating the hemodynamic effects of short-term NaNO2 infusion.Methods and Results—Twenty-five patients with severe chronic HF were recruited. Eight received short-term (5 minutes) intravenous NaNO2 at 10 μg/kg/min and 17 received 50 μg/kg/min with measurement of cardiac hemodynamics. During infusion of 50 μg/kg/min, left ventricular stroke volume increased (from 43.22±21.5 to 51.84±23.6 mL; P=0.003), with marked falls in pulmonary vascular resistance (by 29%; P=0.03) and right atrial pressure (by 40%; P=0.007), but with only modest falls in mean arterial blood pressure (by 4 mm Hg; P=0.004). The increase in stroke volume correlated with the increase in estimated trans-septal gradient (=pulmonary capillary wedge pressure–right atrial pressure; r=0.67; P=0.003), suggesting relief of diastolic ventricular interaction as a contributory mechanism. Directionally similar effects were observed for the above hemodynamic parameters with 10 μg/kg/min; this was significant only for stroke volume, not for other parameters.Conclusions—This first-in-human HF efficacy/safety study demonstrates an attractive profile during short-term systemic NaNO2 infusion that may be beneficial in decompensated HF and warrants further evaluation with longer infusion regimens.

Biomechanics of the right ventricle in health and disease (2013 Grover Conference series).

Right ventricular (RV) function is a major determinant of the symptomatology and outcome in pulmonary hypertension. The normal RV is a thin-walled flow generator able to accommodate large changes in venous return but unable to maintain flow output in the presence of a brisk increase in pulmonary artery pressure. The RV chronically exposed to pulmonary hypertension undergoes hypertrophic changes and an increase in contractility, allowing for preserved flow output in response to peripheral demand. Failure of systolic function adaptation (homeometric adaptation, described by Anrep's law of the heart) results in increased dimensions (heterometric adaptation; Starling's law of the heart), with a negative effect on diastolic ventricular interactions, limitation of exercise capacity, and vascular congestion. Ventricular function is described by pressure-volume relationships. The gold standard of systolic function is maximum elastance (E max), or the maximal value of the ratio of pressure to volume. This value is not immediately sensitive to changes in loading conditions. The gold standard of afterload is arterial elastance (E a), defined by the ratio of pressure at E max to stroke volume. The optimal coupling of ventricular function to the arterial circulation occurs at an E max/E a ratio between 1.5 and 2. Patients with severe pulmonary hypertension present with an increased E max, a trend toward decreased E max/E a, and increased RV dimensions, along with progression of the pulmonary vascular disease, systemic factors, and left ventricular function. The molecular mechanisms of RV systolic failure are currently being investigated. It is important to refer biological findings to sound measurements of function. Surrogates for E max and E a are being developed through bedside imaging techniques.

The shape and function of the left ventricle in Ebstein's anomaly

BackgroundLeft ventricular (LV) failure is common in Ebstein's anomaly, though remains poorly understood. We investigated whether shape deformity impacts LV function. MethodsThree-dimensional models of the right ventricle (RV) and LV from 29 adult Ebstein's patients and nine normal subjects were generated from cardiac magnetic resonance image tracings. LV end diastolic (ED) shape, systolic function, septal motion and ventricular interaction were analyzed. ResultsLV ED volume index was normal in Ebstein's (75±19 vs. 78±11ml/m2 in normals, p=0.50) but the LV was basally narrowed and modestly dilated apically. LV function was reduced globally (ejection fraction (EF) 41±7 vs. 57±5% in normals, p<0.0001) and regionally (decreased mean segment displacement at end systole (ES) in 12/16 segments, basal Z-scores −2.1 to −1.0). Septal dyskinesis was suggested by outward mean segment displacement in at least one basal septal segment in 25 patients (86%) but refuted by septal thickening in 14 (48%), normal septal curvature at ED and ES, and by visually evident basal LV anterior translation in 27 patients (93%). LV EF correlated better with normalized tricuspid annular plane systolic excursion (r=0.70) than with RV EF (r=0.42) or RVEDVI (r=0.18). ConclusionsAlthough the Ebstein's LV has preserved volume, it exhibits basal narrowing, modest apical dilation and global hypokinesis. The apparent basal septal dyskinesis observed in most patients is likely attributable to anterior cardiac translation rather than true paradoxical motion. LV EF is unaffected by RV volume, correlating well instead with RV longitudinal shortening.

A Cardiovascular Mathematical Model of Graded Head-Up Tilt

A lumped parameter model of the cardiovascular system has been developed and optimized using experimental data obtained from 13 healthy subjects during graded head-up tilt (HUT) from the supine position to . The model includes descriptions of the left and right heart, direct ventricular interaction through the septum and pericardium, the systemic and pulmonary circulations, nonlinear pressure volume relationship of the lower body compartment, arterial and cardiopulmonary baroreceptors, as well as autoregulatory mechanisms. A number of important features, including the separate effects of arterial and cardiopulmonary baroreflexes, and autoregulation in the lower body, as well as diastolic ventricular interaction through the pericardium have been included and tested for their significance. Furthermore, the individual effect of parameter associated with heart failure, including LV and RV contractility, baseline systemic vascular resistance, pulmonary vascular resistance, total blood volume, LV diastolic stiffness and reflex gain on HUT response have also been investigated. Our fitted model compares favorably with our experimental measurements and published literature at a range of tilt angles, in terms of both global and regional hemodynamic variables. Compared to the normal condition, a simulated congestive heart failure condition produced a blunted response to HUT with regards to the percentage changes in cardiac output, stroke volume, end diastolic volume and effector response (i.e., heart contractility, venous unstressed volume, systemic vascular resistance and heart rate) with progressive tilting.

Influence of RV Restrictive Physiology on LV Diastolic Function in Children after Tetralogy of Fallot Repair

Restrictive right ventricular (RV) physiology is a common finding after tetralogy of Fallot repair. Via diastolic ventricular interaction, RV filling characteristics may influence left ventricular (LV) filling. The aim of this study was to analyze the effect of RV diastolic physiology on LV diastolic properties. This was a retrospective study including 112 pediatric patients after tetralogy of Fallot repair who underwent full echocardiographic evaluations. Restrictive RV physiology was defined as the presence of end-diastolic forward flow in the main pulmonary artery as detected in at least three consecutive cardiac cycles. RV and LV diastolic function was assessed by analyzing mitral or tricuspid inflow patterns, pulmonary venous flow traces, and pulsed tissue Doppler velocities at the tricuspid and mitral annuli. The mean age at the time of study was 12.9 ± 3.2 years. Restrictive RV physiology was identified in 58 of 112 patients (52%). Patients with RV restriction had larger right atrial and RV dimensions, as well as increased left atrial length and left atrial indexed volume compared with nonrestrictive patients. No differences were found in LV dimensions. Although parameters reflecting early LV diastolic filling (mitral E velocity, lateral annular E' velocity, isovolumetric relaxation time, and E/E' ratio) were not different between the restrictive and nonrestrictive patients, those reflecting late filling were different, with a significantly higher pulmonary venous A-wave reversal velocity and duration in the restrictive group (P < .001). Also, the difference between pulmonary venous A-wave reversal and mitral valve A-wave duration was higher in the restrictive group (P = .0007). End-diastolic forward flow in the main pulmonary artery is associated with larger RV dimensions in pediatric patients with postoperative tetralogy of Fallot. The presence of end-diastolic forward flow was not associated with other differences in RV diastolic parameters but with more pronounced pulmonary venous reversals and larger left atrial size. This indicates that ventricular diastolic interaction affects LV filling pressures.

Diastolic ventricular interaction in patients after atrial switch for transposition of the great arteries: A speckle tracking echocardiographic study

BackgroundWe tested the hypothesis that diastolic ventricular interaction occurs after atrial switch operation for transposition of the great arteries (TGA) and that subpulmonary LV diastolic function is influenced by septal geometry. MethodsTwenty-nine patients (male 19) after atrial switch operation for TGA aged 20.8±4.1years and 27 healthy controls were studied. Two-dimensional longitudinal systolic strain, systolic (SRs), early diastolic (SRe), and late diastolic (SRa) strain rates of both ventricles were determined using speckle tracking echocardiography. Early diastolic trans-atrioventricular velocity (E) and myocardial early diastolic myocardial velocity (e) at the ventricular free wall–annular junction were measured. Geometry of the morphologic left ventricle was quantified by the diastolic eccentricity index (EI). ResultsIn both systemic and subpulmonary ventricles, SRe and SRa were significantly lower and trans-atrioventricular E/e ratios higher in patients than controls (all p<0.001). In patients, RV SRe correlated with left ventricular (LV) SRe (r=0.49, p=0.008), and RV SRa correlated with LV SRa (r=0.46, p=0.01). Significant leftward shifting of the septum in patients was reflected by the greater LV EI (p<0.001). In patients, LV EI correlated with age- and sex-adjusted z score of LV end-diastolic volume. As a group, LV EI correlated negatively with LV SRe (r=−0.62, p<0.001) and LV SRa (r=−0.51, p<0.001), and positively with mitral E/e ratio (r=0.33, p=0.02). ConclusionsSystemic RV diastolic dysfunction occurs after atrial switch operation and correlates with subpulmonary LV diastolic dysfunction. The observed diastolic ventricular interaction may potentially be mediated through alteration of septal geometry.

The Relationship of Right- and Left-Sided Filling Pressures in Patients With Heart Failure and a Preserved Ejection Fraction

Although right-sided filling pressures often mirror left-sided filling pressures in systolic heart failure, it is not known whether a similar relationship exists in heart failure with preserved ejection fraction. Eleven subjects with heart failure with preserved ejection fraction underwent right heart catheterization at rest and under loading conditions manipulated by lower body negative pressure and saline infusion. Right atrial pressure (RAP) was classified as elevated when >or=10 mm Hg and pulmonary capillary wedge pressure (PCWP) when >or=22 mm Hg. If both the RAP and the PCWP were elevated or both not elevated, they were classified as concordant; otherwise, they were classified as discordant. Correlation of RAP and PCWP was determined by a repeated measures model. Among 66 paired measurements of RAP and PCWP, 44 (67%) had a low RAP and PCWP and 8 (12%) a high RAP and PCWP, yielding a concordance rate of 79%. In a sensitivity analysis performed by varying the definition of elevated RAP (from 8 to 12 mm Hg) and PCWP (from 15 to 25 mm Hg), the mean+/-SD concordance of RAP and PCWP was 76+/-10%. The correlation coefficient of RAP and PCWP for the overall cohort was r=0.86 (P<0.0001). Right-sided filling pressures often reflect left-sided filling pressures in heart failure with preserved ejection fraction, supporting the role of estimation of jugular venous pressure to assess volume status in this condition.

VENTRICULAR INTERACTION AND CARDIAC PATHOLOGIES IN A THICK SHELL MODEL OF CARDIAC CHAMBER DEFORMATION

Ventricular interdependence is an important part of heart function, and hence a key mediator of most pathological consequences of its impairment. It can only be explained by accounting for overall chamber deformation as well as cardiac dimensions and nonlinear material properties. Further, clinically useful interpretation of imaging data about pathological alterations in chamber geometry is hampered by lack of understanding of its significance in cardiac function. A model has been developed which describes the ventricles and septum as portions of ellipsoid shells, allowing structural characterization of diastolic ventricular interaction over arbitrary ranges of chamber pressures and volumes as well as intrathoracic pressures. Chamber configuration is derived as a function of pressure gradients by combining shell element equilibrium equations through static boundary conditions applied at the sulcus. Coupling coefficients between state variables are then calculated by letting the system evolve quasistatically through the solution space. The model is used to simulate a number of cardiac pathologies (constrictive pericarditis, restrictive myocarditis, left/right free wall and septal hypertrophy, left dilatative cardiomyopathy) and quantify their effect on ventricular pressure–pressure coupling as well as diastolic pressure–volume relationships. Results match experimental observations where available. The model can aid in interpreting diagnostic data about chamber geometry in a quantitative manner, and the differential effect of cardiac pathologies with otherwise similar phenomenology on ventricular interaction can serve as a discriminating diagnostic criterion.

What about the other two-thirds of the cardiac cycle?

Diastolic dysfunction is a relatively new clinical diagnosis being made in patients where the observed echocardiographic findings are deemed to be consistent with abnormalities of left ventricular (LV) filling. Left ventricular filling is dependent on the complex interaction of three processes: LV relaxation, LV compliance, and left atrial (LA) contraction. Left ventricular relaxation is an active process involving the uptake of Ca into the sarcoplasmic reticulum by the sarcoendoplasmic reticulum Ca ATPase pump and removal of Ca from the cell by way of the sodium-calcium exchanger. Sarcoendoplasmic reticulum Ca ATPase pump expression and activity is reduced in the cardiomyocyte (and diastolic function is altered) with the onset of senescence, hypertrophy, and heart failure. Left ventricular compliance is a measure of the relationship between LV volume and LV pressure development during LV filling (dV/dp). Left ventricular compliance is influenced by: 1) the presence of ventricular hypertrophy; 2) the functional state of the right ventricle (direct diastolic ventricular interaction), since both ventricles share the septum as a common wall; and 3) the properties of the pericardium. Abnormal LV compliance is a feature of longstanding poorly-controlled hypertension, right ventricular dysfunction, and pericardial disease. In the presence of abnormal LV relaxation and/or compliance, LA contraction assumes a key role in maintaining LV filling. Under physiological conditions in youthful individuals, atrial contraction contributes approximately 20% of the total filling volume of the LV; whereas, in patients with LV diastolic dysfunction, LA contraction may account for over 50% of LV volume at enddiastole. Absence of LA contraction, as occurs with the development of atrial fibrillation, is a harbinger of heart failure and is a marker of an increased risk of premature death. The occurrence of abnormal LV relaxation and compliance, as a consequence of hypertensive heart disease, is one of the most common determinants of LA enlargement, poor LA contractile function, and LA dysrhythmia development. It is difficult, if not impossible, to individually assess the components of LV filling in humans; however, relatively precise global estimates of diastolic function can be performed following cardiac catheterization. This approach is invasive, time consuming, and not without risk. In reality, both our knowledge of diastolic function in the broader clinical environment and our interest in the topic did not materialize until the introduction of pulse wave Doppler echocardiography. Pulse wave Doppler echocardiography allows the timing and amplitude of the blood flow and tissue velocity profiles within the heart to be ascertained and graphically displayed. Extensive research has determined which blood flow/tissue velocity profile patterns are considered normal and which appear to be characteristic of diastolic dysfunction. The mitral inflow velocity profile, one of the earliest patterns studied, offers a relatively simple example of the deductive reasoning underlying the evolution of Doppler derived diastolic function assessment. Under ‘‘normal’’ circumstances, flow velocity across the mitral valve is biphasic, i.e., greater during early diastole (E wave) than during subsequent atrial contraction (A wave). In the presence of mild diastolic dysfunction associated with impaired ventricular relaxation, the early diastolic passive flow velocity is reduced while the flow velocity associated with atrial contraction is enhanced (reversed E/A ratio). It is clear, however, that many factors B. A. Finegan, MB (&) Department of Anesthesiology and Pain Medicine, University of Alberta, 8-120 Clinical Sciences Building, Edmonton, AB T6G 2G3, Canada e-mail: chassist@ualberta.ca

Rebuttal from Drs. Warburton and Gledhill

Rebuttal from Drs. Warburton and Gledhill

Rechtsherzinsuffizienz und Cor pulmonale

Whereas the right ventricle tolerates volume loads without any substantial increase of the pressure in the pulmonary circulation by recruiting capacitance vessels and capillaries, it possesses only small contractile reserves and reacts unadapted with right ventricular dysfunction. Its size and pressure load are relevant factors for prognosis of all forms of pulmonary hypertension, in particular if linked to left-sided heart failure. Differentiation of pulmonary hypertension according to the Venice classification is highly important. Right-sided ventricular heart failure worsens left ventricular hemodynamics due to reduced ejection fraction and in addition due to direct diastolic ventricular interaction in which left ventricular diastolic dysfunction increases even though the left ventricular systolic function is still intact. Right ventricular ejection fraction <40% is an important predictor of prognosis after myocardial infarction or chronic stages of left ventricular heart failure. The most important noninvasive diagnostic method is transthoracic echocardiography with determination of the Tei index and Doppler echocardiographic estimation of pulmonary artery pressure. Chronic obstructive pulmonary disease is the most frequent cause of cor pulmonale. While long-term oxygen therapy in patients with COPD and cor pulmonale and for example the administration of endothelin receptor antagonists in patients with idiopathic pulmonary hypertension is beneficial, the therapeutic use of drugs effective for left-sided heart failure is very limited in patients with right ventricular dysfunction.

Diastolic ventricular interactions in endurance-trained athletes during orthostatic stress

Enhanced left-ventricular (LV) compliance is a common adaptation to endurance training. This adaptation may have differential effects under conditions of altered venous return. The purpose of this investigation was to assess the effect of cardiac (un)loading on right ventricular (RV) cavity dimensions and LV volumes in endurance-trained athletes and normally active males. Eight endurance-trained (Vo(2max), 65.4 +/- 5.7 ml.kg(-1).min(-1)) and eight normally active (Vo(2max), 45.1 +/- 6.0 ml.kg(-1).min(-1)) males underwent assessments of the following: 1) Vo(2max), 2) orthostatic tolerance, and 3) cardiac responses to lower-body positive (0-60 mmHg) and negative (0 to -80 mmHg) pressures with echocardiography. In response to negative pressures, echocardiographic analysis revealed a similar decrease in RV end-diastolic cavity area in both groups (e.g., at -80 mmHg: normals, 21.4%; athletes, 20.8%) but a greater decrease in LV end-diastolic volume in endurance-trained athletes (e.g., at -80 mmHg: normals, 32.3%; athletes, 44.4%; P < 0.05). Endurance-trained athletes also had significantly greater decreases in LV stroke volume during lower-body negative pressure. During positive pressures, endurance-trained athletes showed larger increases in LV end-diastolic volume (e.g., at +60 mmHg; normals, 14.1%; athletes, 26.8%) and LV stroke volume, despite similar responses in RV end-diastolic cavity area (e.g., at +60 mmHg: normals, 18.2%; athletes, 24.2%; P < 0.05). This investigation revealed that in response to cardiac (un)loading similar changes in RV cavity area occur in endurance-trained and normally active individuals despite a differential response in the left ventricle. These differences may be the result of alterations in RV influence on the left ventricle and/or intrinsic ventricular compliance.

Ventricular-Arterial and Ventricular-Ventricular Interactions and Their Relevance to Diastolic Filling

Chronic heart failure is a common clinical problem, and, until recently, attention has focused predominantly on those patients with reduced left ventricular (LV) systolic function, as evidenced by a reduced LV ejection fraction. However, nearly half of all patients thought clinically to have heart failure have a "preserved" LV ejection fraction, variously defined as greater than 40% to 45% ("heart failure with normal ejection fraction" syndrome). The interaction of the heart with the systemic vasculature, termed ventricular-arterial coupling, is a key determinant of cardiovascular performance. The capacity of the body to augment cardiac output, regulate systemic blood pressure, and respond appropriately to elevations in heart rate and preload depends on both the properties of the heart and the properties of the vasculature into which the heart ejects blood. Although the marked increase of arterial and cardiac stiffness with aging can maintain ventricular-vascular coupling within a normal range, it does have detrimental effects on hemodynamic stability and cardiac reserve. Patients with heart failure with normal ejection fraction have been shown to have both arterial and ventricular stiffening, resulting in enhanced pressure-load dependence and sensitivity of blood pressure to circulating volume and diuretics. There is also indirect evidence to suggest that on exercise, increased external constraint to LV filling (as a result of diastolic ventricular interaction and pericardial constraint) may contribute to impaired use of the Starling mechanism in this group of patients.

Diastolic ventricular interaction: from physiology to clinical practice

The ventricles share a common septum and, therefore, the filling of one influences the compliance of the other. This phenomenon is known as direct diastolic ventricular interaction. The interaction is noticeably increased when the force exerted by the surrounding pericardium is raised, which is termed pericardial constraint. In healthy individuals, pericardial constraint is minor in the resting state. When right ventricular volume-to-pressure ratio acutely increases, however, such as during exercise, massive pulmonary embolism, or right ventricular infarction, notable diastolic ventricular interaction occurs. In this setting, the measured left ventricular intracavitary diastolic pressure overestimates the true left ventricular filling pressure, because the effect of external forces must be subtracted. Although growth of the pericardium can be a feature of chronic cardiac enlargement, here we review the evidence of the importance of diastolic ventricular interaction in certain acute and chronic disease processes, including heart failure.

Diastolic Ventricular Interactions in Endurance Athletes During Lower Body Positive and Negative Pressure

Increased left ventricular (LV) compliance is one of many cardiovascular adaptations to aerobic exercise training. Enhanced LV compliance may lead to larger end-diastolic volumes and stroke volumes during exercise, ultimately allowing for greater aerobic performance. However, greater LV compliance may be detrimental during negative orthostatic stress, contributing to the reduced orthostatic tolerance seen in endurance athletes. Diastolic ventricular interactions may play an important role in determining LV compliance. Previous research has shown that the volume in one ventricle can directly influence the volume in the opposite ventricle during acute alterations of end-diastolic volume. PURPOSE: To simultaneously assess right (RV) and LV volumes during lower body positive (LBPP) and negative pressure (LBNP), and to compare the responses of endurance athletes with normally active individuals. METHODS: Eight male endurance athletes (VO2 max 65.4 ± 5.7 mL/kg/min) and eight normally active males (VO2 max 45.1 ±6.0 mL/kg/min) underwent three experimental days: 1) assessment of VO2 max, 2) an orthostatic tolerance test, and 3) LBPP (0 to +60 mmHg) and LBNP (0 to −80 mmHg) during which time echocardiographic assessment of LV and RV dimensions were made. ReSUlT S: Seven out of eight endurance athletes did not complete the orthostatic tolerance test due to signs of presyncope, whereas all of the normally active individuals completed the test. Echocardiographic analyses revealed that there were no group differences in the RV response to either LBPP or LBNP; both groups increased or decreased to the same extent. However, there was a differential group response in LV volume during lower body pressures (p<0.05). For example, during LBNP of-80 mmHg the endurance athletes had a reduction of end-diastolic volume of approximately 50 mL, whereas the normally active participants decreased by 25 mL. Conversely, during +60 mmHg the endurance athletes had an increase in LV end-diastolic volume of 25 mL compared to a 10 mL increase in the normally active individuals (p<0.05). CONCLUSIONS: The greater increase (or reduction) in LV volume found in the endurance athletes despite a similar group response in the RV indicates that less diastolic ventricular interaction occurred in the endurance athletes. Less interaction would contribute to the greater LV compliance found in endurance athletes. This finding may partially account for the ability of endurance athletes to utilize the Frank-starling mechanism to a greater extent during exercise, yet be less tolerant of negative orthostatic stress.