Ashwin Prakash

Magnetic Resonance Imaging Predictors of Coarctation Severity

Background—MRI is increasingly used for anatomic assessment of aortic coarctation (CoA), but its ability to predict the transcatheter pressure gradient, considered the reference standard for hemodynamic severity, has not been studied in detail. This study evaluated the ability of MRI to distinguish between mild versus moderate and severe CoA as determined by cardiac catheterization. Methods and Results—The clinical, MRI, and catheterization data of 31 subjects referred for assessment of native or recurrent CoA were reviewed retrospectively. Patients were divided into 2 groups on the basis of peak coarctation gradient by catheterization: <20 mm Hg (n=12) and ≥20 mm Hg (n=19). Patients with cardiac index <2.2 L · min−1 · m−2 by catheterization were excluded. By logistic regression analysis, the following variables simultaneously predicted coarctation gradient ≥20 mm Hg: (1) smallest aortic cross-sectional area (adjusted for body surface area) measured by planimetry from gadolinium-enhanced 3D magnetic resonance angiography (OR 1.71 for 10 mm2/m2 decrease, P=0.005) and (2) heart rate–corrected mean flow deceleration in the descending aorta measured by phase-velocity cine MRI (OR 1.68 for 100 mL/s1.5 increase, P=0.018). For the combination of these variables, a predicted probability >0.38 had 95% sensitivity, 82% specificity, 90% positive and negative predictive values, and an area under the receiver-operator characteristics curve of 0.938. In a subsequent validation study, the prediction model correctly classified 9 of 10 patients, with no false-negatives. Conclusions—The combination of anatomic and flow data obtained by MRI provides a sensitive and specific test for predicting catheterization gradient ≥20 mm Hg.

Myocardial Fibrosis Identified by Cardiac Magnetic Resonance Late Gadolinium Enhancement is Associated with Adverse Ventricular Mechanics and Ventricular Tachycardia Late After Fontan Operation

OBJECTIVES The purpose of this study was to evaluate the relationship between myocardial fibrosis identified by cardiac magnetic resonance (CMR) and ventricular performance and arrhythmias in patients late after the Fontan operation. BACKGROUND Patients who have undergone the Fontan palliation may develop ventricular dysfunction and arrhythmias, but the mechanisms and risk factors are poorly defined. METHODS All patients who have had a Fontan operation and a CMR study with the myocardial delayed-enhancement technique from January 2002 to November 2008 were retrospectively identified. RESULTS Of 90 patients (mean age at study was 23.1 +/- 10.9 years), 25 (28%) had positive late gadolinium enhancement (LGE) in the ventricular myocardium. Patients with positive LGE had lower mean ejection fraction (45% vs. 56%; p < 0.001), increased median end-diastolic volume (100 ml/body surface area [BSA](1.3) vs. 82 ml/BSA(1.3); p = 0.004), increased median ventricular mass(i) (63 g/BSA(1.3) vs. 45 g/BSA(1.3); p < 0.001), higher frequency of regional wall motion abnormalities (52% vs. 28%; p = 0.05), and higher frequency of nonsustained ventricular tachycardia (NSVT) (36% vs. 11%; p = 0.01). Multivariate regression analysis demonstrated that more extensive positive LGE, expressed as percent LGE of total myocardial mass, was associated with lower ejection fraction (p = 0.002), increased end-diastolic volume (p < 0.001), increased mass(i) (p < 0.001), and a higher frequency of NSVT (odds ratio 1.2; 95% confidence interval: 1.1 to 1.4; p = 0.006). CONCLUSIONS In this cohort of late Fontan survivors, myocardial fibrosis was common and associated with adverse ventricular mechanics and a higher prevalence of NSVT. Further studies are warranted to examine the utility of LGE for risk stratification and treatment of ventricular arrhythmia and dysfunction in Fontan patients.

Arrhythmias in a contemporary fontan cohort: prevalence and clinical associations in a multicenter cross-sectional study.

OBJECTIVES Our aim was to examine the prevalence of arrhythmias and identify independent associations of time to arrhythmia development. BACKGROUND Since introduction of the Fontan operation in 1971, long-term results have steadily improved with newer modifications. However, atrial arrhythmias are frequent and contribute to ongoing morbidity and mortality. Data are lacking regarding the prevalence of arrhythmias and risk factors for their development in the current era. METHODS The Pediatric Heart Network Fontan Cross-Sectional study evaluated data from 7 centers, with 520 patients age 6 to 18 years (mean 8.6 +/- 3.4 years after the Fontan operation), including echocardiograms, electrocardiograms, exercise testing, parent-reported Child Health Questionnaire (CHQ) results, and medical history. RESULTS Supraventricular tachycardias were present in 9.4% of patients. Intra-atrial re-entrant tachycardia (IART) was present in 7.3% (32 of 520). The hazard of IART decreased until 4 to 6 years post-Fontan, and then increased with age thereafter. Cardiac anatomy and resting heart rate (including marked bradycardia) were not associated with IART. We identified 3 independent associations of time to occurrence of IART: lower CHQ physical summary score (p < 0.001); predominant rhythm (p = 0.002; highest risk with paced rhythm), and type of Fontan operation (p = 0.037; highest risk with atriopulmonary connection). Time to IART did not differ between patients with lateral tunnel and extracardiac conduit types of Fontan repair. Ventricular tachycardia was noted in 3.5% of patients. CONCLUSIONS Overall prevalence of IART was lower in this cohort (7.3%) than previously reported. Lower functional status, an atriopulmonary connection, and paced rhythm were determined to be independently associated with development of IART after Fontan. (Relationship Between Functional Health Status and Ventricular Performance After Fontan-Pediatric Heart Network; NCT00132782).

Comparison of Echocardiographic and Cardiac Magnetic Resonance Imaging Measurements of Functional Single Ventricular Volumes, Mass, and Ejection Fraction (from the Pediatric Heart Network Fontan Cross-Sectional Study)

Assessment of the size and function of a functional single ventricle (FSV) is a key element in the management of patients after the Fontan procedure. Measurement variability of ventricular mass, volume, and ejection fraction (EF) among observers by echocardiography and cardiac magnetic resonance imaging (CMR) and their reproducibility among readers in these patients have not been described. From the 546 patients enrolled in the Pediatric Heart Network Fontan Cross-Sectional Study (mean age 11.9 +/- 3.4 years), 100 echocardiograms and 50 CMR studies were assessed for measurement reproducibility; 124 subjects with paired studies were selected for comparison between modalities. Interobserver agreement for qualitative grading of ventricular function by echocardiography was modest for left ventricular (LV) morphology (kappa = 0.42) and weak for right ventricular (RV) morphology (kappa = 0.12). For quantitative assessment, high intraclass correlation coefficients were found for echocardiographic interobserver agreement (LV 0.87 to 0.92, RV 0.82 to 0.85) of systolic and diastolic volumes, respectively. In contrast, intraclass correlation coefficients for LV and RV mass were moderate (LV 0.78, RV 0.72). The corresponding intraclass correlation coefficients by CMR were high (LV 0.96, RV 0.85). Volumes by echocardiography averaged 70% of CMR values. Interobserver reproducibility for the EF was similar for the 2 modalities. Although the absolute mean difference between modalities for the EF was small (<2%), 95% limits of agreement were wide. In conclusion, agreement between observers of qualitative FSV function by echocardiography is modest. Measurements of FSV volume by 2-dimensional echocardiography underestimate CMR measurements, but their reproducibility is high. Echocardiographic and CMR measurements of FSV EF demonstrate similar interobserver reproducibility, whereas measurements of FSV mass and LV diastolic volume are more reproducible by CMR.

Design and rationale of a randomized trial comparing the Blalock-Taussig and right ventricle-pulmonary artery shunts in the Norwood procedure

OBJECTIVE The initial palliative procedure for patients born with hypoplastic left heart syndrome and related single right ventricle anomalies, the Norwood procedure, remains among the highest risk procedures in congenital heart surgery. The classic Norwood procedure provides pulmonary blood flow with a modified Blalock-Taussig shunt. Improved outcomes have been reported in a few small, nonrandomized studies of a modification of the Norwood procedure that uses a right ventricle-pulmonary artery shunt to provide pulmonary blood flow. Other nonrandomized studies have shown no differences between the two techniques. METHODS The Pediatric Heart Network designed a randomized clinical trial to compare outcomes for subjects undergoing a Norwood procedure with either the right ventricle-pulmonary artery or modified Blalock-Taussig shunt. Infants with a diagnosis of single, morphologically right ventricle anomaly who are undergoing a Norwood procedure are eligible for inclusion in this study. The primary outcome is death or cardiac transplant 12 months after random assignment. Secondary outcomes include postoperative morbidity after Norwood and stage II palliation procedures, right ventricular function and pulmonary arterial growth at stage II palliation, and neurodevelopmental outcomes at 14 months old. Incidence of adverse events will also be compared between treatment groups. CONCLUSION This study will make an important contribution to the care of patients with hypoplastic left heart syndrome and related forms of single, morphologically right ventricle. It also establishes a model with which other operative interventions for patients with congenital cardiovascular malformations can be evaluated in the future.

Characterization of cardiac tumors in children by cardiovascular magnetic resonance imaging: a multicenter experience.

OBJECTIVES The aim of this study was to report the results of an international multicenter experience of cardiac magnetic resonance imaging (MRI) evaluation of cardiac tumors in children, each with histology correlation or a diagnosis of tuberous sclerosis, and to determine which characteristics are predictive of tumor type. BACKGROUND Individual centers have relatively little experience with diagnostic imaging of cardiac tumors in children, because of their low prevalence. The accuracy of cardiac MRI diagnosis on the basis of a pre-defined set of criteria has not been tested. METHODS An international group of pediatric cardiac imaging centers was solicited for case contribution. Inclusion criteria comprised: 1) age at diagnosis ≤18 years; 2) cardiac MRI evaluation of cardiac tumor; and 3) histologic diagnosis or diagnosis of tuberous sclerosis. Data from the cardiac MRI images were analyzed for mass characteristics. On the basis of pre-defined cardiac MRI criteria derived from published data, 3 blinded investigators determined tumor type, and their consensus diagnoses were compared with histologic diagnoses. RESULTS Cases (n = 78) submitted from 15 centers in 4 countries had the following diagnoses: fibroma (n = 30), rhabdomyoma (n = 14), malignant tumor (n = 12), hemangioma (n = 9), thrombus (n = 4), myxoma (n = 3), teratoma (n = 2), and paraganglioma, pericardial cyst, Purkinje cell tumor, and papillary fibroelastoma (n = 1, each). Reviewers who were blinded to the histologic diagnoses correctly diagnosed 97% of the cases but included a differential diagnosis in 42%. Better image quality grade and more complete examination were associated with higher diagnostic accuracy. CONCLUSIONS Cardiac MRI can predict the likely tumor type in the majority of children with a cardiac mass. A comprehensive imaging protocol is essential for accurate diagnosis. However, histologic diagnosis remains the gold standard, and in some cases malignancy cannot be definitively excluded on the basis of cardiac MRI images alone.

Multimodality Noninvasive Imaging for Assessment of Congenital Heart Disease

Major advances in the field of pediatric cardiology and cardiac surgery over the last several decades have led to a dramatic improvement in survival rates for most forms of congenital heart disease (CHD). For example, hypoplastic left heart syndrome, a previously lethal defect, now has early survival rates up to 90% at major centers.1 These improved outcomes have produced a growing population of survivors with complex CHD who are now reaching adulthood (Figure 1). During this period, improvements in surgical and medical treatments have been accompanied by developments in diagnostic modalities. Echocardiography has replaced catheterization as the primary diagnostic modality, and it is now uncommon for newborn infants to undergo catheterization for purely diagnostic purposes. Although echocardiography remains the bedrock of noninvasive cardiac imaging, the array of diagnostic modalities and techniques available continue to grow and this has spawned the specialty of “noninvasive cardiac imaging” and the need for the “cardiac imager” to be adept in all the different modalities. Figure 1. Percentage of patients under the age of 1 year (grey bars) and over the age of 18 years (black bars) undergoing echocardiography at Children’s Hospital Boston from 1983 through 2006. Note the reverse trends of these age groups reflecting the steady increase in the proportion of adult patients with congenital heart disease. Although the absolute number of infants undergoing echocardiography during this time period has increased, their proportion has steadily declined. Echocardiography, cardiac magnetic resonance (CMR), and cardiac computed tomography (CCT) are the primary modalities used for noninvasive cardiac imaging in patients with CHD. Nuclear scintigraphy is used in selected circumstances. The Table summarizes the strengths and weaknesses of each modality. Figure 2 shows temporal trends in utilization for the various noninvasive cardiac imaging techniques at our center. It is clear that echocardiography is the most frequently …

Cardiac Magnetic Resonance Parameters Predict Transplant-Free Survival in Fontan Patients

Background—Several clinical risk factors for death and heart transplantation have been identified in patients with Fontan circulation. It is unknown whether cardiac magnetic resonance (CMR) measurements of ventricular size and function are independently associated with these outcomes and further improve risk stratification. Methods and Results—Data on patients with Fontan circulation who had a CMR study from January 2002 to January 2011 were retrospectively reviewed. The end point was time to death or listing for heart transplantation after the CMR study. The median age of the 215 patients was 18.3 years (25th, 75th percentiles: 14, 26) with a median age at Fontan of 3.6 years (2.3, 7.1). During a median post-CMR follow-up period of 4.1 years (2.6, 6.2), 24 patients (11%) reached the end point: 20 deaths, 3 transplantations, and 1 transplantation listing. In a multivariable Cox regression model with clinical parameters only, protein-losing enteropathy was associated with transplantation-free survival. A multivariable model, including clinical and CMR parameters, showed that in addition to protein-losing enteropathy, ventricular indexed end-diastolic volume >125 mL/body surface area raised to the 1.3 power was associated with transplantation-free survival. A likelihood-ratio test comparing the 2 models showed that the addition of indexed end-diastolic volume resulted in a significantly improved end point prediction (P<0.001)—C-index increased from 0.63 to 0.79. Conclusions—CMR-derived ventricular indexed end-diastolic volume is an independent predictor of transplantation-free survival in patients late after the Fontan operation and adds incremental value over clinical symptoms alone for risk stratification.

Cardiac magnetic resonance parameters predict transplantation-free survival in patients with fontan circulation.

Background—Several clinical risk factors for death and heart transplantation have been identified in patients with Fontan circulation. It is unknown whether cardiac magnetic resonance (CMR) measurements of ventricular size and function are independently associated with these outcomes and further improve risk stratification. Methods and Results—Data on patients with Fontan circulation who had a CMR study from January 2002 to January 2011 were retrospectively reviewed. The end point was time to death or listing for heart transplantation after the CMR study. The median age of the 215 patients was 18.3 years (25th, 75th percentiles: 14, 26) with a median age at Fontan of 3.6 years (2.3, 7.1). During a median post-CMR follow-up period of 4.1 years (2.6, 6.2), 24 patients (11%) reached the end point: 20 deaths, 3 transplantations, and 1 transplantation listing. In a multivariable Cox regression model with clinical parameters only, protein-losing enteropathy was associated with transplantation-free survival. A multivariable model, including clinical and CMR parameters, showed that in addition to protein-losing enteropathy, ventricular indexed end-diastolic volume >125 mL/body surface area raised to the 1.3 power was associated with transplantation-free survival. A likelihood-ratio test comparing the 2 models showed that the addition of indexed end-diastolic volume resulted in a significantly improved end point prediction (P<0.001)—C-index increased from 0.63 to 0.79. Conclusions—CMR-derived ventricular indexed end-diastolic volume is an independent predictor of transplantation-free survival in patients late after the Fontan operation and adds incremental value over clinical symptoms alone for risk stratification.

Interstudy variability in cardiac magnetic resonance imaging measurements of ventricular volume, mass, and ejection fraction in repaired tetralogy of fallot: A prospective observational study

To assess the interstudy variability of cardiac magnetic resonance imaging (CMR) parameters of ventricular size and function in repaired tetralogy of Fallot (TOF).