Fate of the liver in the survivors of adult heart transplant for a failing Fontan circulation.

The Fontan circulation has inherent long-term vulnerabilities such that adult Fontan patients now comprise the largest, most rapidly growing subgroup of adult congenital heart disease referred for transplant assessment. Almost all have Fontan Associated Liver Disease (FALD). There is an absence of mid to late hepatic outcome data after heart transplant alone. Therefore, we analyzed outcomes of survivors of heart only transplant in patients with failing Fontan circulation. Including all 10 of our adult Fontan patients surviving >1 year after isolated heart transplant, we report evolution of their clinical features, bloodwork, hemodynamic data, and liver ultrasound findings over a median of 4.7 years. Nonprogression of FALD, resolution of ascites and freedom from hepatocellular carcinoma in the mid-term highlight the outcomes in this selected group once normal cardiac output and venous pressures are established by heart transplant.

Evaluation of a comprehensive cardiovascular magnetic resonance protocol in young adults late after the arterial switch operation for d-transposition of the great arteries.

BACKGROUND: In adults with prior arterial switch operation (ASO) for d-transposition of the great arteries, the need for routine coronary artery assessment and evaluation for silent myocardial ischemia is not well defined. In this observational study we aimed to determine the value of a comprehensive cardiovascular magnetic resonance (CMR) protocol for the detection of coronary problems in adults with prior ASO for d-transposition of the great arteries. METHODS: Adult ASO patients (≥18 years of age) were recruited consecutively. Patients underwent a comprehensive stress perfusion CMR protocol that included measurement of biventricular systolic function, myocardial scar burden, coronary ostial assessment and myocardial perfusion during vasodilator stress by perfusion CMR. Single photon emission computed tomography (SPECT) was performed on the same day as a confirmatory second imaging modality. Stress studies were visually assessed for perfusion defects (qualitative analysis). Additionally, myocardial blood flow was quantitatively analysed from mid-ventricular perfusion CMR images. In unclear cases, CT coronary angiography or conventional angiography was done. RESULTS: Twenty-seven adult ASO patients (mean age 23 years, 85% male, 67% with a usual coronary pattern; none with a prior coronary artery complication) were included in the study. CMR stress perfusion was normal in all 27 patients with no evidence of inducible perfusion defects. In 24 cases the coronary ostia could conclusively be demonstrated to be normal. There was disagreement between CMR and SPECT for visually-assessed perfusion defects in 54% of patients with most disagreement due to false positive SPECT. CONCLUSIONS: Adult ASO survivors in this study had no CMR evidence of myocardial ischemia, scar or coronary ostial abnormality. Compared to SPECT, CMR provides additional valuable information about the coronary artery anatomy. The data shows that the asymptomatic and clinically stable adult ASO patient has a low pre-test probability for inducible ischemia. In this situation it is likely that routine evaluation with stress CMR is unnecessary.

Relation of right ventricular mechanics to exercise tolerance in children after tetralogy of Fallot repair.

BACKGROUND: Progressive right ventricular (RV) dysfunction and exercise intolerance are common problems after tetralogy of Fallot (TOF) repair. We investigated RV myocardial deformation and dyssynchrony in children after TOF repair and their association with exercise capacity. METHODS: Asymptomatic children after TOF repair were investigated by 2-dimensional speckle tracking echocardiography, magnetic resonance, and metabolic exercise study. Patients with RV outflow obstruction were excluded. Peak RV longitudinal strain and strain rate (SR) and dyssynchrony (RV intraventricular delay) were compared with healthy controls. Associations between RV strain, dyssynchrony, and exercise capacity were analyzed. RESULTS: Thirty-nine (81%) of 48 TOF patients and 40 healthy controls had adequate RV strain imaging. The TOF patients had moderately dilated RVs and normal RV ejection fraction. Right ventricular peak systolic strain (-23.2% ± 5.1% vs -28.5% ± 8.5%, P < .001) and SR (-1.46 ± 0.68 vs -2.1 ± 0.8, P < .001) were reduced in TOF patients compared with controls. Right ventricular intraventricular delay was higher in TOF patients (146.0 ± 159 vs 71.0 ± 92 milliseconds, P = .008). Decreased RV strain and SR were associated with increased RV dyssynchrony (strain parameter estimate [PE] 6.31 [2.30], P = .007; SR [PE] 11.32 [3.84], P = .004). Increased RV-left ventricular delay was associated with prolonged QRS duration (PE 0.13 [0.058], P = .03) and reduced RV ejection fraction (PE -2.95 [1.275], P = .02). Reduced RV peak SR was associated with decreased exercise peak oxygen uptake (PE 0.14 [0.07], P = .04). CONCLUSIONS: After repair of TOF, asymptomatic children have reduced RV deformation in association with RV dyssynchrony and reduced exercise tolerance.

Determinants and functional impact of restrictive physiology after repair of tetralogy of Fallot: new insights from magnetic resonance imaging.

BACKGROUND: The presence of end-diastolic forward flow (EDFF) in the pulmonary arteries is commonly regarded as a hallmark of restrictive physiology of the right ventricle (RV) which, in turn, has been associated with a better long-term prognosis in patients after TOF repair. However, controversy persists over the beneficial clinical consequences of restrictive physiology. We aimed at determining the clinical relevance of restrictive physiology late after TOF repair. METHODS: Fifty magnetic resonance examinations of 50 patients (age 13.0 ± 2.8 years, 26 males) with repaired TOF were evaluated. The patients were divided into: Group-1 with and Group-2 without EDFF; Group-A with smaller RVs (<170 ml/m2) and Group-B with larger RVs (≥ 170 ml/m2). Maximum oxygen consumption as percent of predicted (VO2max-pred) at a recent exercise test was recorded. RESULTS: Groups-1 and 2 did not differ with regard to their right ventricular end-diastolic volume, pulmonary regurgitant volume, or QRS duration. Patients in Group-1 had a higher VO2max-pred than patients in Group-2 (70.3% versus 54.7% of predicted, p<0.01). In Group-1A versus 2A (RV<170 ml/m(2), with and without EDFF) this difference persisted, but in Group B there was no difference in VO2max-pred between patients with and without EDFF. The flow volume of EDFF correlated with VO2max-pred (r=0.444, p=0.007). CONCLUSIONS: End-diastolic forward flow measured by magnetic resonance is present in patients with small and large RVs. The presence of EDFF is associated with better exercise tolerance, but only in patients with relatively small RVs.

Impaired right and left ventricular diastolic myocardial mechanics and filling in asymptomatic children and adolescents after repair of tetralogy of Fallot.

AIMS: After tetralogy of Fallot (TOF) repair patients have right ventricular (RV) dysfunction and reduced exercise tolerance. Diastolic dysfunction may be important but is as yet poorly characterized. The early diastolic strain rate (SR) is a measure of ventricular relaxation, and may be useful to assess diastolic mechanics in TOF. We hypothesized that children after TOF repair have diastolic dysfunction and dyssynchrony by this measure, and sought to determine their relationship with pulmonary regurgitation (PR), RV enlargement, and aerobic exercise capacity. METHODS AND RESULTS: We prospectively recruited asymptomatic children after TOF repair. RV and PR volumes were measured by magnetic resonance imaging; Doppler and tissue Doppler indices by echocardiography and RV and left ventricular (LV) early diastolic SR by two-dimensional speckle tracking. Exercise peak oxygen consumption (VO(2)) was determined using bicycle ergometry. Results were compared with healthy controls. We studied 53 TOF patients and 49 age-matched controls. TOF patients had significant PR (2.05 ± 1 L/m(2)) with moderate RV dilatation (157 ± 39 mL/m(2)), low-normal RV ejection fraction (49 ± 8.8%), and moderate QRS prolongation (141 ± 23 ms). The RV outflow gradient was 21.7 ± 16.0 mmHg. Patients had RV diastolic dysfunction vs. controls [reduced tricuspid valve (TV) E/A ratio, E' velocity, and longitudinal diastolic SR; increased right atrial volume and TV E/E' ratio]. LV early diastolic radial and circumferential SR were lower in TOF patients in association with more PR [parameter estimate (PE) 0.177 standard error (SE) (0.08) mL/m(2), P = 0.02] and higher RV volumes [(PE) 0.005 (0.002)mL/m(2), P = 0.01]. Diastolic dyssynchrony was not different in TOF patients vs. controls. CONCLUSION: TOF patients have RV and LV diastolic dysfunction associated with RV enlargement and reduced early filling. SR imaging may be useful to quantify early myocardial diastolic dysfunction in these children.

Impaired left ventricular myocardial mechanics and their relation to pulmonary regurgitation, right ventricular enlargement and exercise capacity in asymptomatic children after repair of tetralogy of Fallot.

BACKGROUND: Left ventricular (LV) dysfunction is common in adults late after repair of tetralogy of Fallot (TOF). The early detection of myocardial dysfunction may be important, but LV myocardial strain and dyssynchrony are not well studied in children with TOF. The objective of this study was to investigate LV strain and dyssynchrony in asymptomatic children and adolescents after contemporary repair of TOF. The hypothesis was that impaired LV myocardial mechanics are related to pulmonary regurgitation, right ventricular (RV) enlargement, and exercise capacity. METHODS: Children and adolescents were prospectively studied after TOF repair. LV regional strain and dyssynchrony were assessed using two-dimensional speckle-tracking echocardiography. Ventricular volumes, ejection fraction, and pulmonary regurgitation were assessed using magnetic resonance imaging. Exercise capacity was determined using metabolic exercise testing. RESULTS: One hundred twenty-four subjects (53 patients with TOF and 71 controls) were studied. Regional circumferential (e.g., basal lateral wall, -15.0 ± 7.0% vs -19.0 ± 7.0%, P = .02) and radial (e.g., basal posterior wall, 32.0 ± 18.0% vs 48.0 ± 21.0%, P < .001) LV strain and longitudinal septal strain (-18.5 ± 3.5% vs -20.2 ± 2.8%, P = .01) were significantly reduced in patients with TOF compared with controls. LV mechanical dyssynchrony indices were not significantly different between groups (e.g., standard deviation of time to peak circumferential strain, 52.5 ± 40.4 vs 50.5 ± 27.1 msec, P = .81). Higher pulmonary regurgitation volume and larger RV end-diastolic volume were associated with decreased LV radial strain (P = .09). There was no association between LV longitudinal, radial, or circumferential dyssynchrony and indexed pulmonary regurgitation flow volume, RV end-diastolic volume, or RV ejection fraction. CONCLUSIONS: LV circumferential and radial strain are significantly reduced in children and adolescents after TOF repair and are associated with pulmonary regurgitation and RV dilatation. Resting LV mechanical dyssynchrony does not appear to contribute to early impaired LV strain in this population.

Early changes in right ventricular function and their clinical consequences in childhood and adolescent dilated cardiomyopathy.

The aim of the paper was to investigate the right ventricle in paediatric dilated cardiomyopathy. We examined 11 patients with dilated cardiomyopathy as well as 12 normal paediatric controls. Cardiac magnetic resonance imaging was performed for ventricular size and function. N-terminal pro-brain natriuretic peptide was collected at this time and the results from the most recent echocardiogram and exercise test were reviewed.We found that patients with dilated cardiomyopathy had significantly faster heart rates, that is, 85 versus 65 beats per minute, lower left ventricular ejection fraction, that is, 42 versus 61%, and right ventricular ejection fraction of 44 versus 54%, lower left and right ventricular stroke volumes, that is, 35.5 versus 49.5 millilitres per square metre and 40.9 versus 56.4 millilitres per square metre, respectively, and lower mitral and tricuspid valve inflow e/a wave velocity ratios of 2.02 versus 2.80 and 1.25 versus 2.58, respectively, than the controls. Tricuspid valve annulus velocity, measured by tissue Doppler echocardiography, correlated with right ventricular ejection fraction (r = 0.60, p = 0.05). Right ventricular ejection fraction and indexed right ventricular end-diastolic volume correlated with N-terminal pro-brain natriuretic peptide (r = -0.67, p = 0.03, r = 0.65, p = 0.04, respectively), and right ventricular ejection fraction correlated with the oxygen uptake at the anaerobic threshold (r = 0.67, p = 0.049). Neither left ventricular ejection fraction nor left ventricular volume correlated with N-terminal pro-brain natriuretic peptide or exercise tolerance. The right ventricular function is decreased in the early stages of dilated cardiomyopathy. Right ventricular size and ejection fraction may be important indicators of sub-clinical cardiac failure and we suggest monitoring them routinely in dilated cardiomyopathy.

Recovery of heart function in children with acute severe heart failure.

BACKGROUND: The prognosis of acute heart failure is such that many children are considered for transplantation. Recovery of severe heart failure in a proportion of patients diagnosed with either dilated cardiomyopathy or myocarditis is well recognized, and this complicates the assessment for transplantation. There is little data on the time scale of recovery of heart function in children. OBJECTIVES: To describe the time course over which echocardiographic improvement of systolic function occurred in a cohort of children who presented in acute heart failure, without structural or metabolic abnormality. METHODS: Children with a first presentation of acute severe heart failure between 1990 and 2005. Time from presentation to the echocardiogram before left ventricular fractional shortening (FS) improved to 20% and 30% (complete recovery) was recorded. RESULTS: Twenty-seven children (11 male) were identified, and all had an initial FS <15%. Twenty-one patients required intravenous inotropes and three patients required extracorporeal membrane oxygenation. Seven patients had been on the active transplant list for a mean duration of 155 days. Four patients had probable viral myocarditis. Mean age at presentation was 15.7 (range, 0.1-72) months. Mean time to an FS of 20% was 3.6 (0.2-18) months and to 30% was 8.9 (0.7-24) months. Complete recovery occurred within 6, 9, 12, 18, and 24 months of presentation in 44%, 55%, 66%, and 96%, respectively. There was no correlation between age of presentation and length of time to recovery. CONCLUSIONS: Complete recovery of left ventricular systolic function is often delayed to more than 1 year from presentation. This may have major implications for timing of transplantation in an era where prolonged mechanical cardiac support is feasible even in infants.

Hypertension after pediatric heart transplantation is primarily associated with immunosuppressive regimen.

BACKGROUND: Hypertension is recognized as prevalent in pediatric cardiac transplant recipients. This study investigated risk factors for this complication and, in particular, the role of immunosuppression. METHODS: Results of 24-hour ambulatory blood pressure monitoring of children surviving more than 1 year after cardiac transplantation were analyzed retrospectively. Subjects were designated either hypertensive or normotensive by comparison with published normal values. To identify factors associated with hypertension, clinical data contemporaneous with 24-hour ambulatory blood pressure monitoring were collected and compared between the groups. RESULTS: In the 51 children studied, the incidence of hypertension was 49%. Hypertensive and normotensive recipients were similar for sex, age at transplantation, time between transplantation and 24-hour ambulatory blood pressure results, and choice of calcineurin inhibitor. In contrast, hypertensive patients were taking significantly more immunosuppressive agents (2.92 vs 2.12 p < 0.01), had higher tacrolimus levels (10 vs 8.1 microg/liter, p = 0.03), and were more likely to be on maintenance prednisone therapy (64% vs 23%, p < 0.01) or regimens including sirolimus (40% vs 12%, p = 0.03). Multiple regression analysis controlling for tacrolimus level showed a combination of prednisone and sirolimus was more strongly associated with hypertension than either agent alone, with an odds ratio of 7.3 (95% confidence interval, 1.5-36.1) vs 4.1 (95% confidence interval, 0.85-26.3). CONCLUSIONS: Hypertension after pediatric cardiac transplantation is a common problem and primarily associated with immunosuppressive regimen.

Left ventricular diastolic mechanical dyssynchrony and associated clinical outcomes in children with dilated cardiomyopathy.

BACKGROUND: We investigated diastolic mechanical dyssynchrony and its relation to clinical status in pediatric dilated cardiomyopathy (DCM). METHODS AND RESULTS: We calculated a diastolic and systolic dyssynchrony index (standard deviation of time to peak tissue early diastolic/systolic velocity in 12 left ventricular segments) in 33 children with DCM and 46 control subjects. A threshold to diagnose diastolic dyssynchrony was determined, and cardiac function and clinical outcomes were compared between DCM patients with and without diastolic dyssynchrony. Left ventricular wall motion was more synchronized in diastole than in systole. The diastolic dyssynchrony index was significantly higher in children with DCM than in control subjects (28.1+/-18.1 versus 9.1+/-3.8 ms, P<0.0001). A 17-ms threshold indicated the presence of diastolic dyssynchrony. Patients who died or underwent transplantation had greater diastolic dyssynchrony (diastolic dyssynchrony index 37.9+/-20.5 versus 22.1+/-13.8 ms, P=0.01), and the rate of transplant-free survival appeared to be worse for DCM patients with diastolic dyssynchrony than for patients with synchronous DCM (hazard ratio 2.98, P=0.11; hazard ratio adjusted for disease duration 2.95, P=0.17). CONCLUSIONS: Left ventricular diastolic mechanical dyssynchrony is common in pediatric DCM, especially in patients who subsequently experience transplantation or death, and may be associated with a decreased length of transplantation-free survival.