Identification of patient variables that are associated with ventricular end-diastolic pressure before the bidirectional Glenn operation.

INTRODUCTION: Systemic ventricular end-diastolic pressure is important in patients with single ventricle heart disease. Predictors of an elevated systemic ventricular end-diastolic pressure prior to bidirectional Glenn operation have been incompletely identified. METHODS: All patients who underwent bidirectional Glenn operation operation at our centre between January 2007 and March 2017 were retrospectively identified and patient variables were extracted. For patients who had undergone Fontan operation at the time of this study, post-Fontan patient variables were also extracted. RESULTS: One-hundred patients were included with a median age at pre-bidirectional Glenn operation catheterisation of 4.5 months. In total, 71 (71%) patients had a systemic right ventricle. At the pre-bidirectional Glenn operation catheterisation, the mean systemic ventricular end-diastolic pressure was higher amongst those with systemic right ventricle compared to left ventricle (9.1 mmHg ± 2.1 versus 7.7 ± 2.7 mmHg, p < 0.01). On univariate analysis, pre-bidirectional Glenn operation systemic ventricular end-diastolic pressure was positively associated with the presence of a systemic right ventricle (p < 0.01), history of recoarctation (p = 0.03), history of Norwood operation (p = 0.04), and ventricular systolic pressure (p < 0.01). On multivariate analysis, systemic ventricular end-diastolic pressure was positively associated with the presence of a systemic right ventricle (p < 0.01) and ventricular systolic pressure (p < 0.01). Amongst those who had undergone Fontan operation at the time of study (n = 49), those with a higher pre-bidirectional Glenn operation systemic ventricular end-diastolic pressure were more likely to have experienced death, transplantation, or listed for transplantation (p = 0.02) and more likely to have had heart failure symptoms (p = 0.04) at a mean time from Fontan of 5.2 years ± 1.3. CONCLUSIONS: In patients undergoing bidirectional Glenn operation operation, the volume-loaded, pre-bidirectional Glenn operation state may expose diastolic dysfunction that has prognostic value.

Anomalous Aortic Origin of Coronary Arteries in the Young: Echocardiographic Evaluation With Surgical Correlation.

OBJECTIVES: This study sought to compare findings from institutional echocardiographic reports with imaging core laboratory (ICL) review of corresponding echocardiographic images and operative reports in 159 patients with anomalous aortic origin of a coronary artery (AAOCA). The study also sought to develop a "best practice" protocol for imaging and interpreting images in establishing the diagnosis of AAOCA. BACKGROUND: AAOCA is associated with sudden death in the young. Underlying anatomic risk factors that can cause ischemia-related events include coronary arterial ostial stenosis, intramural course of the proximal coronary within the aortic wall, interarterial course, and potential compression between the great arteries. Consistent protocols for diagnosing and evaluating these features are lacking, potentially precluding the ability to risk stratify patients based on evidence and plan surgical strategy. METHODS: For a prescribed set of anatomic AAOCA features, percentages of missing data in institutional echocardiographic reports were calculated. For each feature, agreement among institutional echocardiographic reports, ICL review of images, and surgical reports was evaluated using the weighted kappa statistic. An echocardiographic imaging protocol was developed heuristically to reduce differences between institutional reports and ICL review. RESULTS: A total of 13%, 33%, and 62% of echocardiograms were missing images enabling diagnosis of intra-arterial course, proximal intramural course, and high ostial takeoff, respectively. There was poor agreement between institutional reports and ICL review for diagnosis of origin of coronary artery, interarterial course, intramural course, and acute angle takeoff (kappa = 0.74, 0.11, -0.03, 0.13, respectively). Surgical findings were also significantly different from those of reports, and to a lesser extent ICL reviews. The resulting protocol contains technical recommendations for imaging each of these features. CONCLUSIONS: Poor agreement between institutional reports and ICL review for AAOCA suggests need for an imaging protocol to permit evidence-based risk stratification and surgical planning. Even then, delineation of echocardiographic details in AAOCA will remain imperfect.

Anomalous aortic origin of a coronary artery: preoperative diagnosis and surgical planning.

BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA), the anomalous coronary artery arises from an inappropriate coronary sinus and travels between the aorta and pulmonary artery. Proper surgical management depends upon correct diagnosis and accurate characterization of the origin and course of the coronary artery. Transthoracic echocardiography (TTE) has been the mainstay for diagnosis, but magnetic resonance imaging (MRI) and computed tomographic angiography (CTA) have been increasingly utilized. In this study, we report the largest series of surgically repaired AAOCA and accuracy of preoperative diagnostic studies. METHODS: A review of 53 consecutive patients (mean age 13.9 years, range 4-65 years) undergoing repair of an AAOCA from 1995 to 2009 was performed. In all, 40 patients were identified with an anomalous right coronary artery (ARCA) from the left sinus of Valsalva, 13 patients had an anomalous left coronary artery (ALCA) arising from the opposite sinus. Symptoms of angina or syncope were present in 58% and 46% of cases with ARCA and ALCA, respectively. RESULTS of preoperative diagnostic testing were compared to actual surgical findings to determine the accuracy of the tests. RESULTS: Lack of an intramural course was observed intraoperatively in 7 cases (5 ARCA and 2 ALCA). Preoperative TTE accurately predicted whether the AAOCA was intramural or extramural in 49 (92.5%) of 53 cases. Magnetic resonance imaging was predictive in 5 (83.3%) of 6 patients and CTA in 11 (64.7%) of 17. Survival was 100%. Complications occurred in 4 (7.5%) of 53 patients (mean follow-up 29 months). Patency was confirmed in 97.7% with TTE, and 23 (95.8%) of 24 patients had a negative postoperative functional study. CONCLUSIONS: Transthoracic echocardiography was found to be very accurate at defining the presence or absence of an intramural course in AAOCA. Both MRI and CTA can provide additional information but may not be as accurate as TTE.

Right ventricular hypertrophy with early dysfunction: A proteomics study in a neonatal model.

OBJECTIVE: Right ventricular hypertrophy and subsequent dysfunction is common in patients with congenital heart defects, but the molecular mechanisms underlying change from adaptive hypertrophy to dysfunction remain elusive. We used the novel technique of proteomics to characterize protein changes in right ventricular myocardium in a neonatal model of right ventricular hypertrophy and early dysfunction. METHODS: Twelve neonatal piglets were equally randomized to pulmonary artery banding (PAB group), or sham operation (thoracotomy without banding). After 4 weeks, right ventricular morphology and function were assessed in vivo using magnetic resonance imaging. Animals were humanely killed. Proteomics of right ventricular myocardium was performed. Purified right ventricular proteins were separated by 2-dimensional difference gel electrophoresis using fluorescent cyanine dyes. After gel imaging, software analysis revealed protein spots differentially expressed between the 2 groups; these spots were excised and identified by mass spectrometry. RESULTS: On magnetic resonance imaging, animals with pulmonary artery banding demonstrated significant right ventricular hypertrophy, cavity dilatation, and mild systolic impairment (right ventricular ejection fraction 39.8% +/- 15% vs 56.7% +/- 10% controls; P < .05). Right ventricular free wall mass on harvest confirmed right ventricular hypertrophy. Proteomic analysis revealed 18 proteins that were significantly differentially expressed: 5 structural proteins, 6 metabolic enzymes, 2 stress proteins, and 5 miscellaneous proteins. Expression of calsarcin-1 and vinculin was increased, as were certain metabolic enzymes, although F(1)-ATPase beta-chain and heat shock protein 70 decreased. CONCLUSIONS: This is the first study characterizing right ventricular protein changes in a large animal model specifically capturing the change from compensated to maladaptive hypertrophy. These findings can guide future work at elucidating the mechanisms in the pathophysiology of neonatal right ventricular hypertrophy and dysfunction.

Cardiac remodeling after enzyme replacement therapy with acid alpha-glucosidase for infants with Pompe disease.

BACKGROUND: Infantile Pompe disease (glycogen storage disease type 2) is a fatal disorder caused by deficiency of acid alpha-glucosidase. This deficiency results in glycogen accumulation in the lysosomes of many tissues including cardiac muscle. The disease is characterized by profound hypotonia, poor growth, organomegaly, and cardiomegaly. Severe hypertrophic cardiomyopathy often is present in early infancy, and most patients die of cardiac or respiratory failure in the first year of life. This report describes the cardiac response of infants with Pompe disease to a phase 2 trial of enzyme replacement therapy (ERT). METHODS: Eight patients with classical infantile Pompe disease were given intravenous recombinant human GAA (rhGAA) for 1 year. Cardiac monitoring included echocardiography, electrocardiograms (ECGs), chest radiographs, and clinical cardiac evaluation at 4, 8, 12, 24, 36, and 52 weeks. At 52 weeks, 6 patients were alive. RESULTS: Most of the treated patients had rapid regression of ventricular hypertrophy in response to ERT, with near normalization of posterior wall thickness, ventricular mass, and ventricular size. Systolic ventricular function was preserved despite rapid changes in ventricular mass and size. Concomitantly, ECGs documented lengthening of the PR interval and decreased ventricular voltages, whereas chest radiographs documented a decreased cardiothoracic ratio. Symptoms of pulmonary congestion were diminished, and survival was improved. CONCLUSION: The cardiovascular system responds quickly and strikingly to ERT with rhGAA, suggesting rapid reversal of excessive glycogen storage in cardiac muscle cells. Changes in ventricular mass and function are maintained throughout 1 year of follow-up evaluation and associated with decreased morbidity and prolonged survival.

A patient with congenital heart disease and ventricular tachycardia: what is the course of the device lead?

A 16-year-old boy with Ebstein's anomaly of the tricuspid valve developed exercise-induced rapid ventricular tachycardia. He had previously undergone tricuspid valvuloplasty and bidirectional cavopulmonary anastamosis due to progressive symptoms. A single-chamber implantable cardioverter-defibrillator was implanted, utilizing a novel transvenous approach to the right ventricle. Technical considerations, risks, and benefits of this approach are discussed.

Right heart dilatation in adults: congenital causes.

OBJECTIVE: The purpose of this article is to illustrate the common congenital cardiac lesions that are characterized by right-sided heart enlargement that may be seen on routine thoracic or cardiac imaging. CONCLUSION: A systematic approach to the evaluation of the right heart and an understanding of the congenital abnormalities causing right chamber enlargement will allow the radiologist to diagnose unsuspected cardiac abnormalities on routine clinical thoracic and cardiac imaging as well as accurately identify these defects on dedicated cardiac CT or MRI examinations.

Utility of fetal echocardiogram in high-risk patients.

AIM: Patients at high risk of fetal congenital heart disease are commonly referred for second trimester fetal echocardiogram. The objective of this study was to evaluate the utility of routine fetal echocardiogram in high-risk patients after the evaluation of the four-chamber/left ventricular outflow tract (LVOT) views during comprehensive second trimester anatomy ultrasound. METHODS: Second trimester comprehensive anatomy ultrasounds, which included a four-chamber/LVOT view, and subsequent fetal echocardiograms carried out at the Duke University Medical Center from January 1995 and July 2002 were reviewed. Those fetal echocardiograms carried out between 17 and 30 weeks gestation were included in the analysis. RESULTS: A total of 725 individual subjects met the inclusion criteria. Twenty-nine fetal echocardiograms were ultimately reported as abnormal. Of these, 19 had an abnormal four-chamber/LVOT view, four had a suboptimal view and six had a normal view. Of the six patients with a normal four-chamber/LVOT, all had been referred for echocardiogram based on the presence of other significant fetal anomalies noted at the time of second trimester anatomy ultrasound (3), documented aneuploidy (2), and significant fetal arrhythmia (1). CONCLUSION: Utility in carrying out fetal echocardiogram was seen in patients with an abnormal four-chamber/LVOT view, a suboptimal view in a high-risk patient, and the presence of other significant fetal abnormalities. Utility was not seen in patients with pre-existing diabetes mellitus.

Pediatric thoracic CT angiography.

One of the principal benefits of contemporary multidetector row computed tomography (MDCT) has been the ability to obtain high-quality data sets for evaluation of the cardiovascular system. The benefits of the greater number of detector rows and submillimeter image thicknesses were quickly recognized and are especially advantageous in children. For example, since imaging is performed so quickly, issues with motion are minimized. This is a substantial benefit of CTA compared with MR imaging, the traditional noninvasive cross sectional modality for pediatric cardiovascular imaging. This, together with faster and more powerful computers, including improved transfer and storage capabilities, offers improved depiction of the heart, great vessels, other vasculature, and adjacent intrathoracic structures in a fashion that is well accepted by clinical colleagues. In order to be successful, however, one must have an understanding of the technology and often unique technical considerations in infants and children. With this familiarity, excellent cardiovascular examinations can be performed even in the most challenging case.

cTnT1, a cardiac troponin T isoform, decreases myofilament tension and affects the left ventricular pressure waveform.

Four isoforms of cardiac troponin T (cTnT), a protein essential for calcium-dependent myocardial force development, are expressed in the human; they differ in charge and length. Their expression is regulated developmentally and is affected by disease states. Human cTnT (hcTnT) isoform effects have been examined in reconstituted myofilaments. In this study, we evaluated the modulatory effects of overexpressing one cTnT isoform on in vitro and in vivo myocardial function. A hcTnT isoform, hcTnT(1), expressed during development and in heart disease but not in the normal adult heart, was expressed in transgenic (TG) mice (1-30% of total cTnT). Maximal active tension measured in skinned myocardium decreased as a function of relative hcTnT(1) expression. The pCa at half-maximal force development, Hill coefficient, and rate of redevelopment of force did not change significantly with hcTnT(1) expression. In vivo maximum rates of rise and fall of left ventricular pressure decreased, and the half-time of isovolumic relaxation increased, with hcTnT(1) expression. Substituting total cTnT charge for hcTnT(1) expression resulted in similar conclusions. Morphometric analysis and electron microscopy revealed no differences between wild-type (non-TG) and TG myocardium. No differences in isoform expression of tropomyosin, myosin heavy chain, essential and regulatory myosin light chains (MLC), TnI, or in posttranslational modifications of mouse cTnT, cTnI, or regulatory MLC were observed. These results support the hypothesis that cTnT isoform amino-terminal differences affect myofilament function and suggest that hcTnT(1) expression levels present during human development and in human heart disease can affect in vivo ventricular function.

Outcome of unroofing procedure for repair of anomalous aortic origin of left or right coronary artery.

BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) from an incorrect sinus of Valsalva is a relatively rare congenital defect and is associated with sudden death. Several surgical techniques have been described to address this defect, but functional outcome has never been addressed. In this report we evaluate a consecutive series of patients treated with unroofing techniques using transthoracic echocardiography, graded exercise testing, and stress echocardiography to assess functional repair. METHODS: Nine consecutive patients (range 7 to 65 years) underwent surgical repair of AAOCA from 1995 to 2001. In all patients the intramural segment was at or below the level of the commissure. All patients underwent a modified unroofing procedure to move the coronary artery orifice to the appropriate sinus. In 2 patients, a new orifice was created without significant unroofing and disruption of the commissure. Patients were evaluated prospectively with exercise electrocardiography testing and by resting and stress echocardiography. RESULTS: Of the 9 patients, 8 presented with symptoms suggestive of ischemia (chest pain, dyspnea on exertion, or syncope). Six patients had anomalous left main coronary artery arising from the right sinus of Valsalva, and 3 patients had anomalous right coronary artery from the left sinus of Valsalva. Transthoracic echocardiography and graded exercise testing was performed in all 9 patients (mean 29 months, range 4 to 85 months) after repair. Of the 9 patients, 8 also underwent stress echocardiography. In 8 of 9 patients the newly created coronary artery ostium was visualized by either two-dimensional echocardiography or color flow Doppler. All patients were symptom free at the time of follow-up. Exercise stress echocardiography was negative in all patients. Of the 8 patients, 7 had normal left ventricular shortening. No patients had regional wall motion abnormalities suggestive of ischemia. All patients were intervention free except 1 patient who developed severe aortic insufficiency and underwent a subsequent Ross procedure 44 months after his initial procedure. CONCLUSIONS: Anomalous origin of a coronary artery from an incorrect sinus of Valsalva is known to be associated with increased risk of sudden death. Surgical correction can be carried out with minimal risk and good anatomic and functional results. Manipulation of the commissure can be avoided by creation of a neo-ostia without extensive unroofing of the intramural segment or manipulation of the intercoronary commissure. This may avoid aortic valve malfunction.

Real-time transmission of pediatric echocardiograms using a single ISDN line.

We tested the adequacy of a videoconferencing system using a single integrated systems digital network (ISDN) line (128 kilobits per second) for the remote diagnosis of children with suspected congenital heart disease (CHD). Real-time echocardiogram interpretation was compared to subsequent videotape review in 401 studies with concordance in 383 (95.5%) studies. A new diagnosis of CHD was made in 98 studies. Immediate patient transfer was arranged based upon a real-time diagnosis in five studies. In 300 studies, a normal diagnosis obviated further evaluation. A single ISDN line is adequate for transmission of pediatric echocardiograms and it allows for remote management of patients with CHD.