Restrictive Right Ventricular Research Articles

Incidence and Type of Right Ventricular Diastolic Dysfunction in Postoperative Tetralogy of Fallot Pediatric Patients

Objective: Assessment of right ventricular (RV) diastolic function in postoperative Tetralogy of Fallot (TOF) patients is not routinely done during intermediate follow-up. We have done this study to assess the incidence and type of RV diastolic dysfunction in these patients. Method: Ninety patients who were less than 18 years and underwent total correction for TOF were analyzed in this study. The incidence and type of RV diastolic dysfunction was measured and the effect of degree of pulmonary regurgitation on RV diastolic function was also seen. Results: The total number of patients with RV diastolic dysfunction was 46 (51.1%). Restrictive RV physiology was seen in 8 patients (8.8%) and the most common type of RV diastolic dysfunction seen was pseudonormal filling, seen in 23 (25.6%) patients. Conclusion: Subclinical RV diastolic dysfunction is present in almost half of the postoperative TOF patients of pediatric age group. The most prevalent form of diastolic dysfunction was pseudonormal filling during intermediate follow-up.

Clinical implications of antegrade diastolic pulmonary artery flow in adults

BackgroundEnd-diastolic opening of the pulmonary valve and subsequent antegrade diastolic pulmonary artery flow (ADPAF) reflect restrictive right ventricular (RV) physiology in children. However, this has attracted little attention in adults. PurposeTo clarify the clinical implications of ADPAF in adults. Methods and ResultsThe study population consisted of 23,049 consecutive adult patients who underwent echocardiography in our hospital between 2008 and 2015. ADPAF was found in 17 patients (0.07%). The simultaneous recording of RV and pulmonary artery pressures revealed marked elevation of RV diastolic pressure, which exceeded pulmonary artery pressure at the time of atrial contraction. These results suggested that ADPAF implies RV restriction. Based on the level of tricuspid annular plane systolic excursion (TAPSE), we classified these patients into two groups: reduced RV function (R-RVF) group (12 patients with TAPSE <17 mm) and preserved RV function (P-RVF) group (5 patients with TAPSE ≥17 mm). In the R-RVF group, four patients died, one patient underwent left ventricular assist device implantation, and two patients underwent unplanned hospitalization for heart failure during follow-up. The R-RVF group had poorer prognosis and higher mortality rate compared with the P-RVF group. ConclusionsADPAF reflects RV restriction in adults. ADPAF suggests a less favorable prognosis in patients with R-RVF.

P4165Influence of restrictive right ventricular physiology in outcomes after transcatheter pulmonary valve implantation in adult patients

Abstract Background A restrictive right ventricular (RV) physiology (r-RVP) is present in almost half of the patients with repaired tetralogy of Fallot (ToF), but its effect on later patients' clinical status is controversial. Purpose Evaluate the outcomes after transcatheter pulmonary valve implantation (TPVI) in patients with restrictive versus non-restrictive RV. Methods Single-center retrospective study of patients who underwent TPVI for pulmonary regurgitation between 2008 and 2017. Electrocardiogram, transthoracic echocardiogram, cardiac magnetic resonance and cardio-pulmonary exercise test were performed previous to TPVI and repeated 12 months after. For statistical analysis restrictive physiology was defined as the presence of end-diastolic forward flow (EDFF) and RVEDVi &lt;150ml/m2. Results Fifty-nine patients, 55 with tetralogy of Fallot, were included. R-RVP was present in 23 patients (39.0%). At the baseline, the majority of the patients were symptomatic, in NYHA functional class II–III (n=48, 81.4%) and with reduced cardiopulmonary performance (VO2max = 20.5mL/min/kg), both worse among patients with r-RVP (p=0.018 and p=0.018). During a mean follow-up of 446.4±226.1 days after TPVI one patient died. BNP levels were not significantly different from baseline. Despite self-reported functional capacity and exercise capacity improvement after TPVI (p&lt;0.001), all parameters remained lower in r-RVP group. One year after TPVI, pulmonary and tricuspid regurgitation decrease significantly, as well as RVEDV, in both groups. However, RV systolic function remained unchanged in both groups. Regarding to the dysrhythmic profile, all patients with need for an implantable cardiac defibrillator and seven of the eight patients requiring radiofrequency ablation for sustained supraventricular arrhythmias during follow-up were in the group without r-RVP (p=0.038). Kaplan-Meier survival curve Conclusion TPVI had a positive impact in clinical status in a cohort of patients with predominant PR regardless the presence of restrictive physiology. Moreover, besides higher VO2max and anaerobic threshold in the non-restrictive group, the magnitude of the improvement was not statistically different between the two groups. Nevertheless, in patients without r-RVP, a peculiar caution has to be focused regarding rhythmic issue during follow-up, despite the TPVI.

Effect of Losartan on Right Ventricular Dysfunction: Results From the Double-Blind, Randomized REDEFINE Trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) in Adults With Repaired Tetralogy of Fallot.

The effect of angiotensin II receptor blockers on right ventricular (RV) function is still unknown. Angiotensin II receptor blockers are beneficial in patients with acquired left ventricular dysfunction, and recent findings have suggested a favorable effect in symptomatic patients with systemic RV dysfunction. The current study aimed to determine the effect of losartan, an angiotensin II receptor blocker, on subpulmonary RV dysfunction in adults after repaired tetralogy of Fallot. The REDEFINE trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) is an investigator-initiated, multicenter, prospective, 1:1 randomized, double-blind, placebo-controlled study. Adults with repaired tetralogy of Fallot and RV dysfunction (RV ejection fraction [EF] <50%) but without severe valvular dysfunction were eligible. Patients were randomly assigned between losartan (150 mg daily) and placebo with target treatment duration between 18 and 24 months. The primary outcome was RV EF change, determined by cardiovascular MRI in intention-to-treat analysis. Of 95 included patients, 47 patients received 150 mg losartan daily (age, 38.0±12.4 years; 74% male), and 48 patients received placebo (age, 40.6±11.4 years; 63% male). Overall, RV EF did not change in patients allocated to losartan (n=42) (44.4±5.1% to 45.2±5.0%) and placebo (n=46) (43.2±6.3% to 43.6±6.9%). Losartan did not significantly improve RV EF in comparison with placebo (+0.51%; 95% confidence interval, -1.0 to +2.0; P=0.50). No significant treatment effects were found on secondary outcomes: left ventricular EF, peak aerobic exercise capacity, and N-terminal pro-brain natriuretic peptide (P>0.30 for all). In predefined subgroup analyses, losartan did not have a statistically significant impact on RV EF in subgroups with symptoms, restrictive RV, RV EF<40%, pulmonary valve replacement, or QRS fragmentation. However, in a post hoc analysis, losartan was associated with improved RV EF in a subgroup (n=30) with nonrestrictive RV and incomplete remodeling (QRS fragmentation and previous pulmonary valve replacement) (+2.7%; 95% confidence interval, +0.1 to +5.4; P=0.045). Losartan had no significant effect on RV dysfunction or secondary outcome parameters in repaired tetralogy of Fallot. Future larger studies may determine whether there might be a role for losartan in specific vulnerable subgroups. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02010905.

Usefulness of Pulmonary Arterial End-Diastolic Forward Flow Late After Tetralogy of Fallot Repair to Predict a “Restrictive” Right Ventricle

The functional significance of pulmonary arterial end-diastolic forward flow (EDFF) in patients with repaired tetralogy of Fallot (rTOF) is not fully understood, with conflicting reports regarding its associations with pulmonary regurgitation (PR), right ventricular (RV) size and function, and so-called restrictive RV physiology. To examine these associations, we retrospectively analyzed 399 patients with rTOF who had contemporaneous echocardiography (Echo) and cardiovascular magnetic resonance (CMR) studies. The median age at TOF repair was 0.7 years (0.21, 2.66), age at CMR was 19.8 years (13.0, 29.4), and interval between Echo and CMR was 48 days (0, 182). Doppler identified EDFF in 122 (31%) patients and CMR in 113 patients (28%). Compared with those without EDFF, patients with EDFF were younger, had greater PR, and higher RV end-diastolic volume, stroke volume, and ejection fraction. Markers of RV restriction such as right atrial size did not differ between groups. On multivariable regression, EDFF was associated with higher RV stroke volume and lower left ventricular end-diastolic volume. The association between Echo and CMR measurements of EDFF was modest (area under the receiver operating characteristic curve = 0.684, r = 0.374, p < 0.001). In conclusion, EDFF was common in this large cohort of patients with rTOF, but its presence and extent varied between Echo and CMR. EDFF was associated with greater PR and larger RV size, but not with markers of poor RV compliance such as right atrial enlargement. Mechanisms beyond RV noncompliance may contribute to the presence of EDFF.

MiR-21 is associated with fibrosis and right ventricular failure.

Combined pulmonary insufficiency (PI) and stenosis (PS) is a common long-term sequela after repair of many forms of congenital heart disease, causing progressive right ventricular (RV) dilation and failure. Little is known of the mechanisms underlying this combination of preload and afterload stressors. We developed a murine model of PI and PS (PI+PS) to identify clinically relevant pathways and biomarkers of disease progression. Diastolic dysfunction was induced (restrictive RV filling, elevated RV end-diastolic pressures) at 1 month after generation of PI+PS and progressed to systolic dysfunction (decreased RV shortening) by 3 months. RV fibrosis progressed from 1 month (4.4% ± 0.4%) to 3 months (9.2% ± 1%), along with TGF-β signaling and tissue expression of profibrotic miR-21. Although plasma miR-21 was upregulated with diastolic dysfunction, it was downregulated with the onset of systolic dysfunction), correlating with RV fibrosis. Plasma miR-21 in children with PI+PS followed a similar pattern. A model of combined RV volume and pressure overload recapitulates the evolution of RV failure unique to patients with prior RV outflow tract surgery. This progression was characterized by enhanced TGF-β and miR-21 signaling. miR-21 may serve as a plasma biomarker of RV failure, with decreased expression heralding the need for valve replacement.

Factors associated with progression of right ventricular enlargement and dysfunction after repair of tetralogy of Fallot based on serial cardiac magnetic resonance imaging.

Although progressive right ventricular (RV) enlargement (RVE) is common in patients with pulmonary regurgitation after tetralogy of Fallot (TOF) repair, the rate of RVE and progression of RV dysfunction varies among patients. The present study aimed to investigate the independent predictors of rapid RVE and RV dysfunction after the repair of TOF, using serial cardiac magnetic resonance imaging (MRI). The study included consecutive patients who underwent serial cardiac MRI more than twice between January 2005 and March 2015 after the repair of TOF. Patients who underwent surgical pulmonary valve implantation or any transcatheter cardiac intervention between two consecutive MRI assessments were excluded. The study patients were divided into rapid RVE and non-rapid RVE groups according to the rate of RVE. The upper first quartile of the patients was considered to have rapid RV dilatation (defined as rapid RVE group). Remaining patients in other three quartiles were included in the non-rapid RVE group. Additionally, the study patients were divided into rapid right ventricular ejection fraction (RVEF) change and non-rapid RVEF change groups according to the rate of change in the RVEF. The groups were compared, and multiple logistic regression analyses were performed to identify the independent risk factors for rapid RVE and RV dysfunction. The study included 116 patients. The mean number of cardiac MRI assessments performed in each patient was 2.8 ± 0.8. The time to the initial MRI assessment after TOF repair was 14.2 ± 10.3 years, and the interval between the initial and last MRI assessments was 4.5 ± 2.2 years. The mean right ventricular end-diastolic volume index (RVEDVi) change rate was 2.7 ± 6.1 ml/m(2)/year. The initial RVEDVi was not different between the rapid RVE and non-rapid RVE groups. Restrictive RV physiology was an independent risk factor for rapid RVE (odds ratio, 3.64; 95% confidence interval, 1.263-10.494; P = 0.02), and a previous palliative shunt procedure was a negative predictor for rapid RVE (odds ratio, 0.08; 95% confidence interval, 0.010-0.778; P = 0.03). We did not find any predictive factors for rapid RV dysfunction. In patients with rapid RV dilatation, restrictive RV physiology might be frequently noted at the initial MRI assessment. Therefore, careful follow-up may be necessary in patients with restrictive RV physiology to determine the optimal timing of pulmonary valve implantation.

Abstract 18046: miR-21 is a Biomarker for Fibrosis and the Progression to Right Ventricular Systolic Failure in a Model of Pulmonary Volume and Pressure Overload

Introduction: Severe pulmonary insufficiency (PI) in combination with moderate pulmonary stenosis (PS) is a common long-term complication after repair of congenital heart diseases such as tetralogy of Fallot, causing progressive right ventricular (RV) dilation and failure. We characterize the physiologic and molecular characteristics of the first murine model of combined RV volume and pressure overload (PI/PS). Methods: Physiologic data was compared between sham controls and PI/PS at 1 and 3 mos. Histopathology and gene, microRNA (miR) and protein expression were assessed in the RV free wall. Plasma miR expression was assessed in children with severe PI/moderate PS vs controls (n=4). Results: Data are presented as sham vs. PI/PS at 1 and 3 mos (*p&lt;0.05). Mice developed diastolic heart failure at 1 mo progressing to systolic heart failure by 3 mos: restrictive RV filling (E/A ratio) (0.7±0.1 vs. 2.1±0.9 and 1.9±0.4*) and elevated RV end-diastolic pressure (2.7±0.3 vs. 7.8±2, and 8.5±2 mmHg*); followed by decreased RV outflow tract shortening (44±2 vs. 39±6 and 29±6%*) and exercise capacity (32±1.1 vs. 28±1.6 and 22±1.9 min*). RV fibrosis increased over time (0 vs. 4.0±2, 3.9±0.2%* sham vs 1 and 3 mos) along with pSMAD/total SMAD expression (0.2±0.1 vs. 0.4±0.1 and 0.6±0.1*), ANP expression (25±15 and 60±27* fold at 1 and 3 mos) and tissue miR-21 expression (2.7±0.3 and 2.9±0.6 fold). However, plasma miR-21 was upregulated with diastolic heart failure and switched to being downregulated with the development of systolic heart failure (2.6±1 and -1.8 ±0.2 fold). Finally, plasma miR-21 expression from children with severe PI/moderate PS at the time of pulmonary valve replacement was downregulated compared to controls (FC -3.6±1.2). Conclusion: We describe a novel murine model of chronic RV volume and pressure overload which recapitulates many aspects of the clinical disease. Gene and protein expression changes suggest enhanced miR-21 and TGF-β signaling as a mediator of RV fibrosis. miR-21 may serve as a novel biomarker of RV fibrosis, with a decline in expression heralding the need for valve replacement. This model provides investigators with a new tool for further evaluation of a form of RV failure unique to children with repaired congenital heart disease.

Restrictive versus Nonrestrictive Physiology Following Repair of Tetralogy of Fallot: Is There a Difference?

Long-term outcome in repaired tetralogy of Fallot (TOF) is related to chronic pulmonary insufficiency (PI), right ventricular (RV) dilation, and deterioration of RV function. The aim of this study was to characterize clinical differences between restrictive and nonrestrictive RV physiology in young patients with repaired TOF. Patients were prospectively enrolled from February 2008 to August 2009. Each had a clinic visit, brain natriuretic peptide assessment, exercise test, cardiac magnetic resonance study, and echocardiographic examination with assessment of regional myocardial mechanics. Consistent antegrade diastolic pulmonary arterial flow with atrial contraction identified restrictive RV physiology. Twenty-nine patients (median age, 12 years; range, 8-33 years; nine male patients) were studied. Twelve had restrictive RV physiology. The median time since initial TOF repair was 12 years (range, 5-27 years). Restrictive physiology appeared more prevalent after transannular patch repair and was not influenced by other demographic features. The restrictive group had more PI (46% vs 28%, P = .002), larger RV end-diastolic volumes (128 vs 98 mL/m(2), P = .046), but similar ejection fractions, brain natriuretic peptide levels, New York Heart Association classes, and exercise capacity. RV basal and mid free wall peak diastolic strain rate differed between groups, negatively correlating with exercise time and positively correlating with PI in patients with restrictive physiology. Restrictive RV physiology correlates with a larger right ventricle and increased PI after TOF repair but does not negatively affect other markers of myocardial health. Diastolic regional RV myocardial mechanics, particularly diastolic velocity and peak diastolic strain rate, differ for postoperative TOF patients with restrictive and nonrestrictive RV physiology; longitudinal study is necessary to understand the relationship of regional myocardial mechanics and patients' clinical status.

Restrictive right ventricular physiology after Tetralogy of Fallot repair is associated with fibrosis of the right ventricular outflow tract visualized on cardiac magnetic resonance imaging

To determine whether the restrictive physiology seen in Tetralogy of Fallot (TOF) patients can be explained by fibrosis of the right ventricular (RV) outflow tract. The aetiology for restrictive RV physiology after TOF repair is not known. TOF patients (n = 31, 13 girls, 10.2 years ± 2.8) were included 9.2 ± 2.9 years after total correction and examined with cardiac magnetic resonance (CMR) and Doppler echocardiography. Cine, flow, and late gadolinium contrast enhanced (LGE) CMR imaging were performed to quantify RV volumes, pulmonary flow and regurgitation (PR), and fibrosis. Healthy children (n = 12) were investigated with CMR of the pulmonary flow. Forward flow during atrial contraction above mean + 2 SD of healthy subjects was set as a marker of restrictive physiology. Four patients were excluded due to suboptimal LGE-CMR. Fisher's exact test was used to determine the association between restrictive physiology and fibrosis. Sixteen patients showed fibrosis in the right ventricular outflow tract (RVOT) on LGE-CMR and 14 of them showed restrictive physiology on CMR. Of the 11 patients without fibrosis in the RVOT, 1 showed restrictive physiology. The odds ratio for RVOT fibrosis in patients with restrictive RV physiology was 70.0 (CI: 5.6-882.7, P < 0.001). The transannular patch repair did not differ between the groups (P = 0.37). The degree of RVOT fibrosis correlated positively with PR (r(2) = 0.38, P < 0.001) and RV volumes (r(2) = 0.51 for end-diastolic volume and r(2) = 0.47 for end-systolic volume, P < 0.001). There is a strong association between the restrictive RV physiology detected on CMR and fibrosis of the RVOT in children after TOF repair.

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.

Relation of Right Ventricular Dilation, Age of Repair, and Restrictive Right Ventricular Physiology With Patient-Reported Quality of Life in Adolescents and Adults With Repaired Tetralogy of Fallot

The present study aimed to determine the predictors of patient-reported quality of life and restrictive right ventricular (RV) physiology in adolescents and adults with repaired tetralogy of Fallot. A total of 62 patients (median age 28.5 years, range 14 to 69) undergoing cardiovascular magnetic resonance imaging completed the Short Form 36-item questionnaire, version 2, a validated quality of life assessment. RV inflow curves were generated from the sum of tricuspid inflow and pulmonary insufficiency. The patient-reported quality of life was comparable to population norms. Patients repaired after 1 year of age showed a strong trend toward a greater likelihood of physical component summary age-adjusted z-score ≤-1 (odds ratio 7.50, 95% confidence interval 0.90 to 62.3, p = 0.06). Patients with a RV ejection fraction of <45% reported decreased physical component summary (p = 0.02) and physical functioning (p = 0.02) scores. The RV end-diastolic volume, pulmonary regurgitation, and diastolic indexes did not predict the quality of life. The indexed RV end-diastolic volume was related to diastolic abnormalities, correlating with a greater peak early filling rate (r = 0.71, p <0.0001), ratio of peak early to atrial filling rates (r = 0.45, p = 0.006), and showing a strong trend with the end-diastolic forward flow in the pulmonary trunk (odds ratio 2.67 for moderate dilation and 3.50 for severe dilation, p = 0.06). Patients who underwent repair before 1 year old were more likely to have end-diastolic forward flow (15 of 17 vs 25 of 42, p = 0.03). In conclusion, the RV ejection fraction and age of repair were the best predictors of quality of life in this population, in whom end-diastolic forward flow and associated diastolic parameters appeared to reflect an overdistended ventricle, which might suggest a role for early pulmonary valve replacement.

Restrictive Right Ventricular Physiology: Its Presence and Symptomatic Contribution in Patients With Pulmonary Valvular Stenosis

The aim of this study was to examine whether restrictive right ventricular (RV) physiology (the presence of antegrade pulmonary arterial flow in late diastole) occurred in patients with moderate to severe isolated pulmonary valvular stenosis (PVS) and to estimate its prevalence and relationship to RV function and patient symptoms. Little is published about RV diastolic performance in adult patients with PVS. A total of 43 consecutive patients (age 44 +/- 10 years) with moderate to severe PVS referred to Royal Brompton Hospital from 2002 to 2005 were retrospectively studied. Patient New York Heart Association (NYHA) functional class was recorded. The RV (lateral tricuspid annulus motion) long-axis movement was measured by M-mode and pulsed-wave (PW) tissue Doppler imaging (TDI). Restrictive RV physiology was assessed by PW Doppler echocardiography. Eighteen patients (42%) had restrictive RV physiology. They were more symptomatic (NYHA functional class 1.8 +/- 0.5 vs. 1.3 +/- 0.5; p < 0.001) and had poorer RV long-axis function (TDI peak systolic velocity 7.3 +/- 2.1 cm/s vs. 9.7 +/- 2.7 cm/s; TDI early diastolic velocity 6.6 +/- 1.6 cm/s vs. 8.5 +/- 2.4 cm/s; RV long-axis systolic amplitude 1.3 +/- 0.2 cm vs. 1.5 +/- 0.3 cm; p < 0.01 for all) compared with other PVS patients despite similar RV ejection fraction, myocardial performance index, and RV systolic pressure. The presence of restrictive RV physiology (odds ratio [OR] 6.05, 95% confidence interval [CI] 1.45 to 10.29; p = 0.01) and peak pulmonary valve pressure gradient (OR 1.07, 95% CI 1.01 to 1.13; p = 0.04) were the 2 independent echocardiographic predictors for decreased exercise tolerance in patients on multivariate analysis. Restrictive RV physiology is common in PVS patients. Its presence is related to a worse deterioration in RV long-axis function and decreased exercise tolerance in patients.

Right ventricular restrictive physiology in repaired tetralogy of Fallot is associated with smaller respiratory variability

Background Long-term outcomes of patients with repaired tetralogy of Fallot (TOF) are known to be related with right ventricular (RV) volume overload, severity of pulmonary insufficiency (PI) and the type of outflow repair. Right ventricular restrictive physiology (RVRP) has also been reported to interfere with several factors influencing the late result in repaired TOF patients. However, the mechanism and physiology of this unique myocardial property in the chronically overloaded right ventricle are not yet clearly understood. Methods We investigated 43 patients after repair of TOF to assess the relationships among biventricular diastolic function, volume characteristics, and influence of respiratory effort. The patients were classified into 3 groups; 15 patients with RVRP and significant PI (RP group, 35%), 19 without RVRP in the presence of significant PI (NR + PI group, 44%), and 9 without RP or significant PI (NR − PI group, 21%). Doppler spectrals obtained by echocardiography from systemic and pulmonary veins, main pulmonary artery (MPA), and both ventricular inlets, and biventricular diastolic function were compared according to the respiratory cycle. Results The RP group revealed higher pulmonary venous systolic/diastolic flow ratio (S/D ratio) and the NR + PI group showed larger velocity-time integral (VTI) ratio of total regurgitant/antegrade flow at the MPA and more respiratory variability in the systemic vein. Conclusion RP is associated with less volume overload of the RV and smaller respiratory variability is also associated with the restrictive RV. The diastolic function and volume status of the RV may influence the diastolic properties of the left heart.

Diastolic Function in Repaired Tetralogy of Fallot at Rest and during Stress: Assessment with MR Imaging

To prospectively assess, with magnetic resonance (MR) imaging, right ventricular (RV) diastolic function after repair of tetralogy of Fallot (TOF) at rest and during pharmacologic stress and to study relationship between main pulmonary artery end-diastolic forward flow (EDFF) (indicative of restrictive RV physiology) and clinical status. Institutional medical ethics committee approval and patient or parent informed consent were obtained. Patients with TOF corrected through the transatrial-transpulmonary approach underwent MR imaging at rest and during dobutamine stress and maximal exercise testing. Two-dimensional (2D) cine volumetric data were acquired. Flow measurements were performed with a standard 2D flow-sensitized sequence. MR imaging flow curves for tricuspid and pulmonary valves were combined into RV time-volume change curves, from which indexes of RV filling were derived. Patient results were compared with published data in control subjects. Student t tests, Mann-Whitney U tests, analysis of covariance, and paired and one-sample t tests were used. Thirty-six patients (mean age at repair, 0.9 year +/- 0.5 [standard deviation]; median age at study inclusion, 17 years [range, 7-23 years]; 26 male and 10 female patients) were included. Abnormalities in RV filling included impaired relaxation (prolonged deceleration time, P = .002; smaller early filling fraction, P = .02) in the entire group compared with published data in healthy control subjects and signs of restriction to RV filling (smaller atrial filling fraction and higher early filling/atrial filling peak ratio, P < .05 for both) in patients with EDFF (n = 24) compared with patients without EDFF (n = 12). Stress response was abnormal in patients with EDFF, who developed impaired RV relaxation not appreciated at rest. Patients with EDFF had more severe pulmonary regurgitation (P < .05) and poorer exercise performance (P < .001). In patients with TOF corrected with currently widely accepted surgical strategies, pulmonary artery EDFF relates to worse clinical state at mid- to long-term follow-up. Dobutamine stress imaging may unmask abnormalities in RV diastolic filling not appreciated with rest imaging alone.

Right Ventricular Diastolic Function After Repair of Tetralogy of Fallot

The objective of this study was quantitate diastolic dysfunction in the postoperative phase of tetralogy of Fallot (TOF) and to correlate it with the type of surgical procedure and clinical parameters. Fifty consecutive patients (mean age, 5.0 years; mean weight, 13.5 kg), operated for TOF during the period November 2004 to May 2005, were prospectively studied [infundibular resection, 23; infundibular resection and transannular patch (TAP), 19; right ventricle --> pulmonary artery conduit, 8). Detailed echocardiography was done on postoperative days 3 and 9 with a focus on Doppler indices of right ventricular (RV) function, Antegrade late diastolic flow in the right ventricular outflow tract (RVOT) was taken as the marker of restrictive RV physiology. The previous parameters were correlated to the type of surgery and clinical indices of RV dysfunction. There was no mortality. Twenty-four patients showed restrictive RV physiology. This finding correlated with lower values of E/A ratio (0.98 +/- 0.17 vs 1.33 +/- 0.49, p < 0.002), tricuspid valve E-wave deceleration time (86.9 +/- 21.7 vs 151.4 +/- 152 msec, p < 0.05), index of myocardial performance (0.15 +/- 0.06 vs 0.26 +/- 0.09, p < 0.001), isovolumic relaxation time (19.4 +/- 17 vs 39+/-30 msec, p < 0.009), and a higher central venous pressure (15.1 +/- 1.5 vs 12.7 +/- 1.9, p < 0.001). Restrictive RV physiology correlated with prolonged intensive case unit (ICU) stay (5.1 +/- 3.7 vs 2.8 +/- 2 days, p < 0.015), longer duration of inotropic support (108.3 +/- 56.2 vs 55.5 +/- 28.3 hours, p < 0.02), and higher dosage of diuretics. RV diastolic dysfunction is demonstrable by Doppler echocardiography in the first week following surgery for TOF and tends to be worse with TAP. Restrictive physiology demonstrated by RVOT pulse Doppler predicts longer duration of inotropic support, prolonged ICU stay, and higher dosage of diuretics.

The right ventricle in Fabry disease

Left ventricular (LV) hypertrophy is a common feature in Fabry disease-related progressive infiltrative hypertrophic cardiomyopathy and affects both men and women, but at different ages. To date, however, little is known about the role of right ventricular (RV) function in Fabry disease. Therefore, this study aimed to investigate the extent of RV involvement in patients with Fabry disease. Echocardiographic examination of the right and left ventricle was carried out in 129 patients (80 women and 49 men) with Fabry disease. RV hypertrophy was present in 46 patients (35.7%). Of these patients, 13 showed signs of severely depressed right systolic function (tricuspid annulus movement < 10 mm and a prolonged RV pre-ejection period/pulmonary ejection time ratio) and six patients showed additional severe depression of parameters of diastolic function (pseudo-normal or restrictive RV filling pattems). Those patients with RV hypertrophy and severely compromised systolic and diastolic function had the highest LV masses (92 +/- 11.7 g/m(2.7)). RV involvement is common in Fabry disease and ultimately progresses to severe systolic and diastolic RV dysfunction. These findings might explain why patients with preserved LV function can develop clinical features such as reduced exercise capacity, organomegaly and lymphoedema.

Negative pressure ventilation as haemodynamic rescue following surgery for congenital heart disease.

A low cardiac output state is an important cause of morbidity and mortality following repair of tetralogy of Fallot (ToF). This is often refractory to conventional measures. The cardiac output of these patients is highly dependent on diastolic pulmonary arterial flow which is enhanced during spontaneous respiration, but much reduced by intermittent positive pressure ventilation (IPPV). We report the successful use of negative pressure ventilation (NPV) as haemodynamic therapy in three children with a low output secondary to restrictive right ventricular (RV) physiology following ToF repair. NPV produced a significant haemodynamic improvement, with increases in cardiac output of greater than 100 % in two of the children. By augmenting pulmonary blood flow, and hence cardiac output, NPV has a role as adjunctive haemodynamic therapy in patients with a low output secondary to diastolic RV dysfunction, in whom early extubation is not possible.

Acute right ventricular restrictive physiology after repair of tetralogy of Fallot: association with myocardial injury and oxidative stress.

Acute right ventricular (RV) restrictive physiology after tetralogy of Fallot repair results in low cardiac output and a prolonged stay in the intensive care unit (ICU). However, its mechanism remains uncertain. In the first 24 hours after tetralogy of Fallot repair (n=11 patients), serial prospective measurements were performed of cardiac troponin T, indexes of NO production (NO(2)(-) and NO(3)(-) combined as NOx), and iron metabolism and antioxidants. RV diastolic function was assessed by transthoracic Doppler echocardiography. Patients who had a long stay in the ICU were characterized by restrictive RV physiology (nonrestrictive group [n=7]: 3.0+/-0.6 days [mean+/-SD]; restrictive group [n=4]: 10.7+/-3.1 days). Troponin T peak concentration and the area under its concentration-time curve (AUC) were higher in the restrictive RV group (peak: restrictive group 17. 0+/-2.8 microg/L, nonrestrictive group 10.4+/-4.6 microg/L, P<0.03; AUC: restrictive group 268.8+/-73.6 microg. h(-1). L(-1), nonrestrictive group 136.2+/-48.3 microg. h(-1). L(-1), P<0.03). Plasma NOx/creatinine concentrations were higher in the restrictive group than the nonrestrictive group at 2 hours after bypass (restrictive group 1.3+/-0.4, nonrestrictive group 0.8+/-0.2; P=0. 04) but were similar by 24 hours. Iron loading peaked 2 to 10 hours after bypass and was more severe in the restrictive group (peak transferrin saturation: restrictive group 83.9+/-13.0%, nonrestrictive group 58.3+/-16.2%, P=0.05; minimum total iron-binding capacity: restrictive group 0.59+/-0.21%, nonrestrictive group 0.76+/-0.06%, P=0.04; minimum iron-binding antioxidant activity to oxyorganic radicals: restrictive group 9. 5+/-22.4%, nonrestrictive group 50.6+/-11.4%, P=0.01). After tetralogy of Fallot repair, acute restrictive RV physiology is associated with greater intraoperative myocardial injury and postoperative oxidative stress with severe iron loading of transferrin.

Early age at repair prevents restrictive right ventricular (RV) physiology after surgery for tetralogy of Fallot (TOF): Diastolic RV function after TOF repair in infancy

Objectives. To assess diastolic right ventricular (RV) physiology after tetralogy of Fallot repair in infancy.Background. Restrictive RV physiology after tetralogy of Fallot repair is related to type of repair, pulmonary regurgitation, and late arrhythmias.Methods. Forty-seven patients were investigated, 27 and 20 patients in Lund and London, respectively. Median age at repair was 0.78 years (0.08–0.99) and median follow-up was 3.0 years (0.08–10.4). Restrictive RV physiology was assessed by Doppler echocardiography.Results. Thirteen patients (28%) had restrictive RV physiology at follow-up, three of 19 patients (16%) with transatrial repair and 10 of 28 patients (32%) with transventricular repair, respectively (p = 0.1). Ten percent of the patients repaired before 6 months of age were restrictive at follow-up, increasing to 38% with repair after 9 months. Transannular patch (TAP) repair was performed in 55% of the patients, including eight of 10 patients (80%) with repair before 6 months of age. Thirty-one percent of the patients with TAP repair were restrictive. These restrictive patients had more severe preoperative pulmonary stenosis (p < 0.05), were older at repair (p < 0.05), and had shorter duration of pulmonary regurgitation (p < 0.001) at follow-up.Conclusions. Restrictive RV physiology is inversely related to age at repair and independent of type of outflow tract repair. Since TAP repair is more common in early repair, and restriction seems to be less frequent, long-term follow-up to assess adverse effects of pulmonary regurgitation is mandatory.