Girish S. Shirali

EAE/ASE recommendations for image acquisition and display using three-dimensional echocardiography.

Roberto M. Lang, MD, FASE*‡, Luigi P. Badano, MD, FESC†‡, Wendy Tsang, MD*, David H. Adams, MD*, Eustachio Agricola, MD†, Thomas Buck, MD, FESC†, Francesco F. Faletra, MD†, Andreas Franke, MD, FESC†, Judy Hung, MD, FASE*, Leopoldo Pérez de Isla, MD, PhD, FESC†, Otto Kamp, MD, PhD, FESC†, Jaroslaw D. Kasprzak, MD, FESC†, Patrizio Lancellotti, MD, PhD, FESC†, Thomas H. Marwick, MBBS, PhD*, Marti L. McCulloch, RDCS, FASE*, Mark J. Monaghan, PhD, FESC†, Petros Nihoyannopoulos, MD, FESC†, Natesa G. Pandian, MD*, Patricia A. Pellikka, MD, FASE*, Mauro Pepi, MD, FESC†, David A. Roberson, MD, FASE*, Stanton K. Shernan, MD, FASE*, Girish S. Shirali, MBBS, FASE*, Lissa Sugeng, MD*, Folkert J. Ten Cate, MD†, Mani A. Vannan, MBBS, FASE*, Jose Luis Zamorano, MD, FESC, FASE†, and William A. Zoghbi, MD, FASE*

Percutaneous Implantation of the Edwards SAPIEN Transcatheter Heart Valve for Conduit Failure in the Pulmonary Position: Early Phase 1 Results From an International Multicenter Clinical Trial

OBJECTIVES The purpose of this study was to evaluate the safety and effectiveness of the Edwards SAPIEN transcatheter heart valve (Edwards Lifesciences LLC, Irvine, California) in the pulmonary position in patients with moderate to severe pulmonary regurgitation with or without stenosis. BACKGROUND Transcatheter pulmonary valve replacement is evolving, but to date, experience has been limited to the Melody valve (Medtronic Inc., Minneapolis, Minnesota). METHODS Eligible patients with dysfunctional right ventricle-to-pulmonary artery conduits were screened if body weight was ≥35 kg and the in situ conduit diameter was ≥16 mm and ≤24 mm. Standardized implantation and follow-up protocols were used. RESULTS Thirty-six patients from 4 centers were recruited between April 2008 and May 2010. Mean body weight was 73.4 ± 22.9 kg. Successful valve deployment was achieved in 33 of 34 attempts (97.1%). Valve migration occurred in 3 patients, with 2 requiring surgical retrieval; however, 1 patient underwent successful perventricular valve implantation. Further intraprocedure complications included pulmonary hemorrhage (n = 2), ventricular fibrillation (n = 1), and stent migration (n = 1). Pullback gradient across the conduit decreased from 26.8 ± 18.4 mm Hg to 11.7 ± 8.0 mm Hg (p < 0.001). The right ventricular/aortic pressure ratio decreased from 0.6 ± 0.2 to 0.4 ± 0.1 (p < 0.001). Peak Doppler gradient across the right ventricular outflow tract decreased from 41.9 ± 27.9 mm Hg to 19.1 ± 13.3 mm Hg (p < 0.001). At 6-month follow-up, all patients were alive. The number of patients with New York Heart Association functional class I increased from 5 at baseline to 27 at follow-up. Pulmonary regurgitation was ≤2+ in 97% of patients. Freedom from reintervention was 97% with 1 patient undergoing elective placement of a second valve due to conduit-induced distortion of the initial implant. CONCLUSIONS Transcatheter pulmonary valve replacement using the Edwards SAPIEN transcatheter heart valve is safe and effective in patients with dysfunctional right ventricle-to-pulmonary artery conduits.

Association of Viral Genome with Graft Loss in Children after Cardiac Transplantation

BACKGROUND The survival of recipients of cardiac allografts is limited by rejection, lymphoproliferative disease, and coronary vasculopathy. The purpose of this study in children who had received heart transplants was to evaluate the cardiac allografts for myocardial viral infections and to determine whether the presence of viral genome in the myocardium correlates with rejection, coronary vasculopathy, or graft loss. METHODS We enrolled heart-transplant recipients 1 day to 18 years old who were undergoing evaluation for possible rejection and coronary vasculopathy. Endomyocardial-biopsy specimens were evaluated for evidence of rejection with the use of standard criteria and were analyzed for the presence of virus by the polymerase chain reaction (PCR). RESULTS PCR analyses were performed on 553 consecutive biopsy samples from 149 transplant recipients. Viral genome was amplified from 48 samples (8.7 percent) from 34 patients (23 percent); adenovirus was found in 30 samples, enterovirus in 9 samples, parvovirus in 5 samples, cytomegalovirus in 2 samples, herpes simplex virus in 1 sample, and Epstein-Barr virus in 1 sample. In 29 of the 34 patients with positive results on PCR (85 percent), an adverse cardiac event occurred within three months after the positive biopsy, and 9 of the 34 patients had graft loss due to coronary vasculopathy, chronic graft failure, or acute rejection. In 39 of the 115 patients with negative results on PCR (34 percent), an adverse cardiac event occurred within three months of the negative PCR finding; graft loss did not occur in any of the patients in this group. The odds of graft loss were 6.5 times as great among those with positive results on PCR (P=0.006). The detection of adenovirus was associated with considerably reduced graft survival (P=0.002). CONCLUSIONS Identification of viral genome, particularly adenovirus, in the myocardium of pediatric transplant recipients is predictive of adverse clinical events, including coronary vasculopathy and graft loss.

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.

Dobutamine stress echocardiography for assessing coronary artery disease after transplantation in children

OBJECTIVES The purpose of this study was to determine the feasibility, safety and diagnostic accuracy of dobutamine stress echocardiography (DSE) for evaluating posttransplant coronary artery disease (TxCAD) in children, and to determine the frequency of selected cardiac events after normal or abnormal DSE. BACKGROUND Posttransplant coronary artery disease is the most common cause of graft loss (late death or retransplantation) after cardiac transplantation (CTx) in children. Coronary angiography, routinely performed to screen for TxCAD, is an invasive procedure with limited sensitivity. The efficacy of DSE for detecting atherosclerotic coronary artery disease is established, but is unknown in children after CTx. METHODS Of the 78 children (median age 5.7 years, range 3 to 18) entered into the study, 72 (92%) underwent diagnostic DSE by means of a standard protocol, 4.6 +/- 1.9 years after CTx. The results of coronary angiography performed in 70 patients were compared with DSE findings. After DSE, subjects were monitored for TxCAD-related cardiac events, including death, retransplantation and new angiographic diagnosis of TxCAD. RESULTS No major complications occurred. Minor complications, most often hypertension, occurred in 11% of the 72 subjects. The sensitivity and specificity of DSE were 72% and 80%, respectively, when compared with coronary angiography. At follow-up (21 +/- 8 months), TxCAD-related cardiac events occurred in 2 of 50 children (4%) with negative DSE, versus 6 of 22 children (27%) with positive DSE (p < 0.01). CONCLUSIONS DSE is a feasible, safe and accurate screening method for TxCAD in children. Positive DSE identifies patients at increased risk of TxCAD-related cardiac events. Negative DSE predicts short-term freedom from such events.

Noncoronary Cardiac Abnormalities Are Associated With Coronary Artery Dilation and With Laboratory Inflammatory Markers in Acute Kawasaki Disease

OBJECTIVES We explored the association of noncoronary cardiac abnormalities with coronary artery dilation and with laboratory inflammatory markers early after Kawasaki disease (KD) diagnosis. BACKGROUND Left ventricular (LV) dysfunction, mitral regurgitation (MR), and aortic root dilation occur early after diagnosis; their associations with coronary artery dilation and inflammatory markers have not been well-described. METHODS Centrally interpreted echocardiograms were obtained at KD diagnosis and 1 and 5 weeks after diagnosis on 198 subjects in the National Institutes of Health-sponsored Pediatric Heart Network KD pulsed steroid trial. Regression models were constructed to investigate the relationships among early LV dysfunction, MR, and aortic root dilation with coronary artery dilation and laboratory inflammatory markers. RESULTS At diagnosis, LV systolic dysfunction was present in 20% of subjects and was associated with coronary artery dilation, seen in 29% (p = 0.004). Although LV dysfunction improved rapidly, LV dysfunction at diagnosis predicted greater odds of coronary artery dilation at 1 and 5 weeks after diagnosis (5-week odds ratio: 2.7, 95% confidence interval: 1.2 to 6.3). At diagnosis, MR was present in 27% of subjects and aortic root dilation was present in 8%; each was associated with larger coronary artery size at diagnosis. Left ventricular dysfunction was associated with higher erythrocyte sedimentation rate and, at diagnosis only, lower serum albumin; MR was associated with higher erythrocyte sedimentation rate and lower albumin at all times. Aortic root size had little association with inflammatory markers. CONCLUSIONS Noncoronary cardiac abnormalities are associated with coronary artery dilation and laboratory evidence of inflammation in the first 5 weeks after KD, suggesting a shared inflammatory mechanism. (Trial of Pulse Steroid Therapy in Kawasaki Disease [A Trial Conducted by the Pediatric Heart Network]; NCT00132080).

The ventricular volume variability study of the Pediatric Heart Network: study design and impact of beat averaging and variable type on the reproducibility of echocardiographic measurements in children with chronic dilated cardiomyopathy.

BACKGROUND Clinical trials often rely on echocardiographic measures of left ventricular size and function as surrogate end points. However, the quantitative impact of factors that affect the reproducibility of these measures is unknown. To address this issue, the National Heart, Lung, and Blood Institute-funded Pediatric Heart Network designed a longitudinal observational study of children with known or suspected dilated cardiomyopathy aged 0 to 22 years from eight pediatric clinical centers. METHODS Clinical data were collected together with 150 echocardiographic indices of left ventricular size and function. Separate observers performed duplicate echocardiographic imaging. Multiple observers performed measurements from three cardiac cycles to enable assessment of intraobserver and interobserver variability. The impacts of beat averaging (BA), observer type (local vs core), and variable type (areas, calculations, dimensions, slopes, time intervals, and velocities) on measurement reproducibility were studied. The outcome measure was percentage error (100 × difference/mean). RESULTS Of 173 enrolled subjects, 131 met criteria for dilated cardiomyopathy. BA, variable type and observer type all influenced percentage error (P < .0001). Core interobserver percentage error (medians, 11.4%, 10.2%, and 9.3% for BA using one, two, and three beats, respectively) was approximately twice the intraobserver percentage error (medians, 6.3%, 4.9%, and 4.2% for BA using one, two, and three beats, respectively). Slopes and calculated variables exhibited high percentage error despite BA. Chamber dimensions, areas, velocities, and time intervals exhibited low percentage error. CONCLUSIONS This comprehensive evaluation of quantitative echocardiographic methods will provide a valuable resource for the design of future pediatric studies. BA and a single core lab observer improve the reproducibility of echocardiographic measurements in children with dilated cardiomyopathy. Certain measurements are highly reproducible, while others, despite BA, are poorly reproducible.

Real-Time Three-Dimensional Echocardiography Is Useful in the Evaluation of Patients with Atrioventricular Septal Defects

Objective: We sought to determine whether three‐dimensional echocardiography (3DE) is useful in the evaluation of patients with atrioventricular septal defect (AVSD). Background: Recent advances in 3DE have enhanced its practicality. We assessed whether 3DE provided new information compared to 2DE among patients with AVSD. Methods: We retrospectively reviewed 52 3DE datasets from 51 patients (median age: 4.6 years, range 0–30 years; median BSA: 0.6 m2, range 0.2–1.9 m2) with any type of AVSD during a 1‐year period. 3DE findings were compared to 2DE and surgical reports. For each study, AVSD was classified by 2DE as one of the following: unrepaired balanced defect, repaired balanced defect with residual lesions, repaired balanced defect without residual lesions, or unbalanced defect. 3DE was graded as (1) Additive: 3DE resulted in a new finding or changed diagnosis; (2) Useful: While useful, 3DE did not result in new findings or changed diagnosis; or (3) Not useful. Results: 3DE on unrepaired balanced AVSD and repaired AVSD with residual lesions was more often additive/useful (33/36; 92%) than on repaired AVSD without residual lesions or unbalanced AVSD (9/16 (56%), P=0.009). 3DE was additive or useful in all three patients with unbalanced AVSD being considered for biventricular repair. Useful information obtained by 3DE included: precise characterization of mitral regurgitation and cleft leaflet, substrate for subaortic stenosis, valve anatomy, and presence and location of additional septal defects. Conclusion: 3DE provides useful and additive information in unrepaired balanced AVSD, repaired AVSD with residual lesions, and unbalanced AVSD under consideration for biventricular repair.

Does a ventriculotomy have deleterious effects following palliation in the Norwood procedure using a shunt placed from the right ventricle to the pulmonary arteries

INTRODUCTION A recent modification to the Norwood procedure involving a shunt placed directly from the right ventricle to the pulmonary arteries may improve postoperative haemodynamics. Concerns remain, however, about the potential problems produced by the required ventriculotomy. METHODS We compared 76 patients with hypoplastic left heart syndrome who underwent the Norwood procedure, 35 receiving a modified Blalock-Taussig shunt and the remaining 41 a shunt placed directly from the right ventricle to the pulmonary arteries. We reviewed their subsequent progress through the second stage of palliation. A single observer graded right ventricular function, and the severity of tricuspid regurgitation, based on blinded review of the most recent echocardiograms prior to the second stage of palliation. RESULTS At the time of catheterization prior to the second stage, patients with a shunt placed from the right ventricle to the pulmonary arteries, rather than a modified Blalock-Taussig shunt, had higher arterial diastolic blood pressure, at 44 versus 40 millimetres of mercury, p equal to 0.02, lower ventricular end diastolic pressures, at 8 versus 11 millimetres of mercury, p equal to 0.0002, and larger pulmonary arteries as judged using the Nakata index, at 270 versus 188 millimetres squared per metres squared, p equal to 0.009. There was no difference in qualitative ventricular systolic function or tricuspid regurgitation between groups. No differences were found between groups during the hospitalization following the second stage of palliation. A trend towards improved survival to the second stage was seen following the construction of a shunt from the right ventricle to the pulmonary arteries. CONCLUSIONS Construction of a shunt from the right ventricle to the pulmonary arteries is associated with lower right ventricular end diastolic pressures, larger pulmonary arterial size, and higher systemic arterial diastolic pressures. No apparent deleterious effects of the right ventriculotomy were observed in terms of qualitative ventricular systolic function or tricuspid regurgitation.

Current issues and perspectives in hypoplasia of the left heart

Hypoplastic left heart syndrome is a rare but serious form of congenital cardiac disease, characterized by underdevelopment of the components of the left heart, rendering the left ventricle non-functional. Its aetiology is largely unknown, but there is certainly a genetic component. Prenatal diagnosis nowadays uncovers about half of cases. Postnatal options for treatment include comfort care, 3-stage palliative surgery, or cardiac transplantation. In this review, we discuss the morphology, possible pathogenetic mechanisms, clinical management, and perspectives of prenatal intervention based on work in animal models.