Marina Hughes

A Multicenter, Randomized Trial Comparing Heparin/Warfarin and Acetylsalicylic Acid as Primary Thromboprophylaxis for 2 Years After the Fontan Procedure in Children

OBJECTIVESnThe purpose of this study was to compare the safety and efficacy of acetylsalicylic acid (ASA) and warfarin for thromboprophylaxis after the Fontan procedure.nnnBACKGROUNDnFontan surgery is the definitive palliation for children with single-ventricle physiology. Thrombosis is an important complication; the optimal thromboprophylaxis strategy has not been determined.nnnMETHODSnWe performed a multicenter international randomized trial of primary prophylactic anticoagulation after Fontan surgery. Patients were randomized to receive for 2 years either ASA (5 mg/kg/day, no heparin phase) or warfarin (started within 24 h of heparin lead-in; target international normalized ratio: 2.0 to 3.0). Primary endpoint (intention to treat) was thrombosis, intracardiac or embolic (all events adjudicated). At 3 months and 2 years after the Fontan procedure, transthoracic and transesophageal echocardiograms were obtained as routine surveillance. Major bleeding and death were primary adverse outcomes.nnnRESULTSnA total of 111 eligible patients were randomized (57 to ASA, 54 to heparin/warfarin). Baseline characteristics for each group were similar. There were 2 deaths unrelated to thrombosis or bleeding. There were 13 thromboses in the heparin/warfarin group (3 clinical, 10 routine echo) and 12 thromboses in the ASA group (4 clinical, 8 routine echo). Overall freedom from thrombosis 2 years after Fontan surgery was 19%, despite thrombosis prophylaxis. Cumulative risk of thrombosis was persistent but varying and similar for both groups (p = 0.45). Major bleeding occurred in 1 patient in each group.nnnCONCLUSIONSnThere was no significant difference between ASA and heparin/warfarin as primary thromboprophylaxis in the first 2 years after Fontan surgery. The thrombosis rate was suboptimal for both regimens, suggesting alternative approaches should be considered. (International Multi Centre Randomized Clinical Trial Of Anticoagulation In Children Following Fontan Procedures; NCT00182104).

The role of cardiovascular magnetic resonance in pediatric congenital heart disease.

Cardiovascular magnetic resonance (CMR) has expanded its role in the diagnosis and management of congenital heart disease (CHD) and acquired heart disease in pediatric patients. Ongoing technological advancements in both data acquisition and data presentation have enabled CMR to be integrated into clinical practice with increasing understanding of the advantages and limitations of the technique by pediatric cardiologists and congenital heart surgeons. Importantly, the combination of exquisite 3D anatomy with physiological data enables CMR to provide a unique perspective for the management of many patients with CHD. Imaging small children with CHD is challenging, and in this article we will review the technical adjustments, imaging protocols and application of CMR in the pediatric population.

Impact of Pulmonary Valve Replacement in Tetralogy of Fallot With Pulmonary Regurgitation: A Comparison of Intervention and Nonintervention

BACKGROUNDnThe timing and indicators for surgical pulmonary valve replacement (PVR) in patients with pulmonary regurgitation (PR) after repair of tetralogy of Fallot (ToF) are controversial. In this study we tested the hypothesis that delaying PVR in patients with ToF and severe PR would lead to short-term progressive deterioration in right ventricular/left ventricular (RV/LV) dimensions or function. We compared PVR-treated patients with matched untreated patients who were eligible for PVR based on hemodynamic status.nnnMETHODSnA current cohort of 87 patients with ToF and free PR serial cardiovascular magnetic resonance (CMR) assessments at a median interval of 1.8 years (interquartile range [IQR], 1.4-2.1) were identified. During this interval, 51 patients had surgical PVR and 36 patients were managed conservatively. Twenty-five patients from each group were matched for comparison using propensity score matching (PSM). RV and LV measurements were assessed by CMR at rest at follow-up.nnnRESULTSnThere was no significant deterioration in RV or LV measurements in the matched untreated patients over a median of 1.8 years. Normalization of right ventricular end-diastolic volume (RVEDV) and end systolic volume (ESV) after PVR occurred in the majority of patients during the study period, and no absolute ceiling beyond which the right ventricle did not normalize could be discerned. In a group of treated patients who were not matchable because of severe baseline characteristics, there was a significant improvement in resting cardiac output (CO) after PVR (from 2.9 to 3.3 L/min/m(2); p = 0.001).nnnCONCLUSIONSnOur data indicate that patients with intermediate RV dilatation and severe PR are at low risk for significant progression in the short term, which can guide the interval for CMR imaging and advise the timing for future PVR.

The relationship of systemic right ventricular function to ECG parameters and NT-proBNP levels in adults with transposition of the great arteries late after Senning or Mustard surgery

Aims Heart failure is common late after Senning or Mustard palliation of transposition of the great arteries (TGA). Although cardiac magnetic resonance (CMR) is the gold standard for evaluating systemic right ventricular performance, additional information regarding heart failure status might be gleaned from the surface ECG and circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. The interrelationships between these heart failure markers were examined in adults late after Mustard and Senning surgery. Methods Thirty-five consecutive adults with Senning or Mustard repair of TGA attending a dedicated congenital heart failure clinic were studied. Assessment included symptom assessment, venous blood sampling for measurement of circulating NT-proBNP levels, surface 12-lead ECG and CMR for the assessment of right ventricular systolic function and determination of indexed right ventricular volumes. Results Mean age was 29±6.5u2005years, 54% had undergone Mustard surgery. Compared with those with uncomplicated surgery, patients with complex surgical history had higher NT-proBNP levels (55±26 vs 20±35u2005pmol/l; p=0.002) and longer QRS duration (116±28u2005ms vs 89±11u2005ms; p=0.0004) while showing no difference in New York Heart Association class and right ventricular function. There was a significant relationship between diastolic and systolic right ventricular volumes and both NT-proBNP levels (r=0.43, p=0.01; r=0.53, p=0.001, respectively) and QRS duration (r=0.47, p=0.004; r=0.53, p=0.001, respectively). Conclusions Circulating NT-proBNP levels and several surface ECG parameters constitute safe, cost-effective and widely available surrogate markers of systemic right ventricular function and provide additional information on heart failure status. Both measures hold promise as prognostic markers and their association with long-term outcome should be determined.

Physiological and Phenotypic Characteristics of Late Survivors of Tetralogy of Fallot Repair Who Are Free From Pulmonary Valve Replacement

Background— Pulmonary valve replacement (PVR) after repair of tetralogy of Fallot is commonly required and is burdensome. Detailed anatomic and physiologic characteristics of survivors free from late PVR and with good exercise capacity are not well described in a literature focusing on the indications for PVR. Methods and Results— Survival and freedom from PVR were tracked in 1085 consecutive patients receiving standard tetralogy of Fallot repair in a single institution from 1964 to 2009. Of 152 total deaths, 100 occurred within the first postoperative year. Surviving patients between 10 and 50 years of age had an annual risk of death of 4 (confidence limit, 2.8–5.4) times that of normal contemporaries. To date, 189 patients have undergone secondary PVR at mean age of 20±13 years (36% of those alive at 40 years of age). A random sample of 50 survivors (age, 4–57 years) free from PVR underwent cardiovascular magnetic resonance, echocardiography, and exercise testing. These patients had mildly dilated right ventricles (right ventricular end-diastolic volume=101±26 mL/m2) with good systolic function (right ventricular ejection fraction=59±7%). Most had exercise capacity within normal range (z peak O2=−0.91±1.3; z E/ CO2=0.20±1.5). In patients >35 years of age with normal exercise capacity, there was mild residual right ventricular outflow tract obstruction (mean gradient, 24±13 mmu2009Hg), pulmonary annulus diameters <0.5z, and unobstructed branch pulmonary arteries. Conclusions— An important proportion of patients require PVR late after tetralogy of Fallot repair. Patients surviving to 35 years of age without PVR and with a normal exercise capacity may have had a definitive primary repair; their right ventricular outflow tracts are characterized by mild residual obstruction and pulmonary annulus diameter <0.5z.

Diffuse myocardial fibrosis in the systemic right ventricle of patients late after Mustard or Senning surgery: an equilibrium contrast cardiovascular magnetic resonance study

AIMSnAfter atrial redirection surgery (Mustard-Senning operations) for transposition of the great arteries (TGA), the systemic right ventricle (RV) suffers from late systolic failure with high morbidity and mortality. Mechanisms of late RV failure are poorly characterized. We hypothesized that diffuse interstitial expansion representing diffuse fibrosis is greater in systemic RVs of patients following Mustard-Senning surgery and that it would be associated with other markers of heart failure and disease severity.nnnMETHODS AND RESULTSnWe used equilibrium contrast cardiovascular magnetic resonance (CMR) imaging to quantify extracellular volume (ECV) in the septum and RV free wall of 14 adults presenting to a specialist clinic late after surgery for TGA (8 Mustard, 6 female, median age 33). These were compared with 14 age-and sex-matched healthy volunteers. Patients were assessed with a standardized CMR protocol, NT-brain natriuretic peptide (NT-proBNP), and cardiopulmonary exercise (CPEX) testing. The mean septal ECV was significantly higher in patients than controls (0.254 ± 0.036 vs. 0.230 ± 0.032; P = 0.03). NT-proBNP positively related to septal ECV (P = 0.04; r = 0.55). The chronotropic index (CI) during CPEX testing negatively related to the ECV (P = 0.04; r = -0.58). No relationship was seen with other CMR or CPEX parameters. R.V free wall ECV was difficult to measure (heavy trabeculation, sternal wires, blood pool in regions of interest) with high and poor inter-observer reproducibility: this analysis was abandoned.nnnCONCLUSIONnSeptal interstitial expansion is seen in adults late after atrial redirection surgery for TGA. It correlates well with NT-proBNP and CI and may have a role in the development of RV systolic impairment. Measuring interstitial expansion in the RV free wall is difficult using this methodology.

Systemic to pulmonary collateral blood flow influences early outcomes following the total cavopulmonary connection

Background Systemic to pulmonary collaterals (SPCs) represent an additional and unpredictable source of pulmonary blood flow in patients with single ventricle physiology following bidirectional superior cavopulmonary connection (BCPC). Understanding their influence on patient outcomes has been hampered by uncertainty about the optimal method of quantifying SPC flow. Objective To quantify SPC flow by cardiac magnetic resonance (CMR) prior to total cavopulmonary connection (TCPC) in order to identify preoperative risk factors and determine influence on postoperative outcomes. Design Single centre prospective cohort study. Setting Tertiary referral centre. Patients 65 patients with single ventricle physiology undergoing CMR for preoperative assessment of TCPC completion underwent quantification of SPC flow. Clinical outcomes of 41 patients in whom TCPC was completed were obtained. Main outcome measures Early post-TCPC clinical outcomes associated with SPC flow were assessed, including postoperative chest drainage volume, postoperative chest drainage duration and length of intensive care and hospital stays. Additionally preoperative covariates associated with SPC flow were assessed including age at BCPC and CMR, SpO2 at BCPC and CMR, ventricle type, pulmonary artery (PA) cross-sectional area and PA pulsatility. Different methods of CMR SPC flow quantification were compared. Results Higher SPC flow was associated with increased postoperative chest drain volume (r=0.51, p=0.001), chest drain duration (r=0.43, p=0.005), and intensive care unit (r=0.32, p=0.04) and log-transformed hospital stays (r=0.31, p=0.048). The effect of SPC flow on outcome was independent of fenestration, ventricle type and function. Preoperative covariates associated with SPC flow included age at BCPC (β=−0.34, p=0.008), SpO2 at time of CMR (β=0.34, p=0.004) and branch PA cross-sectional area (β=−0.26, p=0.036), model R2=0.34. Moreover, patients with pulsatile pulmonary blood flow had lower SPC flow than those without (0.8 vs 1.3u2005l/min/m2 p=0.012). SPC flow calculated by the difference between pulmonary venous return and pulmonary artery flow (l/min/m2) showed greatest association with preoperative covariates and strongest correlation with postoperative outcomes compared with other methods of quantification. Conclusions CMR can provide an effective measurement of SPC flow prior to TCPC. Young age at BCPC, high preoperative oxygen saturation and smaller PAs are associated with increased SPC flow, which may promote increased postoperative pleural drainage and lengthen recovery.

Introduction to cardiac imaging in infants and children: Techniques, potential, and role in the imaging work-up of various cardiac malformations and other pediatric heart conditions

The increasing prevalence of congenital heart disease (CHD) can be attributed to major improvements in diagnosis and treatment. Although echocardiography is the most commonly used imaging modality for diagnosis and follow-up of subjects with CHD, the evolution of cardiovascular magnetic resonance (MR) imaging and increasingly computed tomography (CT) does offer new ways to visualize the heart and the great vessels. The development of cardiovascular MR techniques allows for a comprehensive assessment of cardiac anatomy and function. This provides information about the long-term sequlae of the underlying complex anatomy, hemodynamic assessment of residual post-operative lesions and complications of surgery. As much of the functional data in CHD patients is usually acquired with invasive X-ray angiography, non-invasive alternatives such as cardiovascular MR (and CT) are desirable. This review evaluates the role of MR imaging in the management of subjects with CHD, particularly detailing recent developments in imaging techniques as they relate to the various CHD diagnoses we commonly encounter in our practice.

Cardiovascular magnetic resonance findings in repaired anomalous left coronary artery to pulmonary artery connection (ALCAPA)

BackgroundAnomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare coronary artery anomaly. This study shows the role of cardiovascular magnetic resonance (CMR) in assessing young patients following surgical repair of ALCAPA.Methods6 patients, aged 9-21 years, with repaired ALCAPA (2 Tackeuchi method, 4 direct re-implantation) underwent CMR because of clinical suspicion of myocardial ischemia. Imaging used short and long axis cine images (assess ventricular function), late-gadolinium enhancement (LGE) (detect segmental myocardial fibrosis), adenosine stress perfusion (detect reversible ischaemia) and 3D whole-heart imaging (visualize proximal coronary arteries).ResultsThe left ventricular (LV) global systolic function was preserved in all patients (mean LV ejection fraction = 62.7% ± 4.23%). The LV volumes were within the normal ranges, (mean indexed LVEDV = 75.4 ± 3.5 ml/m2, LVESV = 31.6 ± 9.4 ml/m2). In 1 patient, hypokinesia of the anterior segments was visualized. Five patients showed sub-endocardial LGE involving the basal, antero-lateral wall and the anterior papillary muscle. Three patients had areas of reversible ischemia. In these 3, 3D whole-heart MRA showed that the proximal course of the left coronary artery was occluded (confirmed with cardiac catheterisation).ConclusionsCMR is a good, non-invasive, radiation-free investigation in the post-surgical evaluation of ALCAPA. In referred patients we show that basal, antero-lateral sub-endocardial myocardial fibrosis is a characteristic finding. Furthermore, stress adenosine CMR perfusion, can identify reversible ischemia in this group, and was indicative of left coronary artery occlusion.

Prevalence of Associated Cardiovascular Abnormalities in 500 Patients With Aortic Coarctation Referred for Cardiovascular Magnetic Resonance Imaging to a Tertiary Center

Coarctation of the aorta (CoA) is a common congenital defect whose overall incidence is 5–8% of all congenital cardiac anomalies. Associated cardiac anomalies have been well described in previous studies examining specific subgroups of CoA patients, particularly infants and necropsy specimens. The majority of studies, conducted from the 1970s to 1980s, excluded older children, adolescents, and adults. Given the advent of improved surgical and interventional techniques, many CoA patients are surviving into adulthood. This study examined a population of 500 CoA patients in the authors’ cardiovascular magnetic resonance imaging (MRI) database involving a population of CoA survivors 5–79xa0years of age. This was to give a new perspective on the prevalence of associated cardiovascular abnormalities including the bicuspid aortic valve, arch hypoplasia, intracardiac shunts, and subaortic stenosis. These associated abnormalities are less prevalent than in previous studies, reflecting a milder spectrum of CoA. Cardiovascular MRI with its multiplanar imaging capabilities and lack of ionizing radiation is safe and suitable for evaluation and follow-up assessment of CoA patients. Evaluation of CoA by MRI should not be confined to the arch, but should include the heart and mediastinal vessels to assess for the presence and severity of any expected or unexpected associated anomalies.