Ventricular arrhythmia risk prediction in repaired Tetralogy of Fallot using personalized computational cardiac models.

BACKGROUND: Adults with repaired tetralogy of Fallot (rTOF) are at increased risk for ventricular tachycardia (VT) due to fibrotic remodeling of the myocardium. However, the current clinical guidelines for VT risk stratification and subsequent implantable cardioverter-defibrillator deployment for primary prevention of sudden cardiac death in rTOF remain inadequate. OBJECTIVE: The purpose of this study was to determine the feasibility of using an rTOF-specific virtual-heart approach to identify patients stratified incorrectly as being at low VT risk by current clinical criteria. METHODS: This multicenter retrospective pilot study included 7 adult rTOF patients who were considered low risk for VT based on clinical criteria. Patient-specific computational heart models were generated from late gadolinium enhanced magnetic resonance imaging (LGE-MRI), incorporating the individual distribution of rTOF fibrotic remodeling in both ventricles. Simulations of rapid pacing determined VT inducibility. Model creation and simulations were performed by operators blinded to clinical outcome. RESULTS: Two patients in the study experienced clinical VT. The virtual hearts constructed from LGE-MRI scans of 7 rTOF patients correctly predicted reentrant VT in the models from VT-positive patients and no arrhythmia in those from VT-negative patients. There were no statistically significant differences in clinical criteria commonly used to assess VT risk, including QRS duration and age, between patients who did and those who did not experience clinical VT. CONCLUSION: This study demonstrates the feasibility of image-based virtual-heart modeling in patients with congenital heart disease and structurally abnormal hearts. It highlights the potential of the methodology to improve VT risk stratification in patients with rTOF.

Computational Identification of Ventricular Arrhythmia Risk in Pediatric Myocarditis.

Children with myocarditis have increased risk of ventricular tachycardia (VT) due to myocardial inflammation and remodeling. There is currently no accepted method for VT risk stratification in this population. We hypothesized that personalized models developed from cardiac late gadolinium enhancement magnetic resonance imaging (LGE-MRI) could determine VT risk in patients with myocarditis using a previously-validated protocol. Personalized three-dimensional computational cardiac models were reconstructed from LGE-MRI scans of 12 patients diagnosed with myocarditis. Four patients with clinical VT and eight patients without VT were included in this retrospective analysis. In each model, we incorporated a personalized spatial distribution of fibrosis and myocardial fiber orientations. Then, VT inducibility was assessed in each model by pacing rapidly from 26 sites distributed throughout both ventricles. Sustained reentrant VT was induced from multiple pacing sites in all patients with clinical VT. In the eight patients without clinical VT, we were unable to induce sustained reentry in our simulations using rapid ventricular pacing. Application of our non-invasive approach in children with myocarditis has the potential to correctly identify those at risk for developing VT.

Appropriate Use Criteria for paediatric echocardiography in an outpatient practice: a validation study.

BACKGROUND: Although transthoracic echocardiography is the dominant imaging modality in CHD, optimal utilisation is unclear. We assessed whether adherence to the paediatric Appropriate Use Criteria for outpatient transthoracic echocardiography could reduce inappropriate use without missing significant cardiac disease. METHODS: Using the Appropriate Use Criteria, we determined the indication and appropriateness rating for each initial echocardiogram performed at our institution during calendar year 2014 (N=1383). Chart review documented ordering provider training, patient demographics, and study result, classified as normal, abnormal, or abnormal motivating treatment within a 2-year follow-up period. We tested whether provider training level or patient age correlated with echocardiographic findings or appropriateness rating. RESULTS: We found that 83.9% of echocardiograms were normal and that 66.7% had an appropriate indication. Nearly all abnormal results and all results motivating treatment were in appropriate studies, giving an odds ratio of 2.73 for an abnormal result if an appropriate indication was present (95% confidence interval 1.92-3.89, p<0.001). None of the remaining initial abnormal results with less than appropriate indications became significant, resulting in treatment over 2 years. Results suggest a potential reduction in imaging volume of as much as 33% with application of the criteria. Cardiologists ordered nearly all studies resulting in treatment but also more echocardiograms with less appropriate indications. Most examinations were in older patients; however, most abnormal results were in patients younger than 1 year. CONCLUSIONS: The Appropriate Use Criteria can be used to safely reduce echocardiography volume while still detecting significant heart disease.

Role of virtual reality in congenital heart disease.

OBJECTIVE: New platforms for patient imaging present opportunities for improved surgical planning in complex congenital heart disease (CHD). Virtual reality (VR) allows for interactive manipulation of high-resolution representations of patient-specific imaging data, as a supplement to traditional 2D visualizations and 3D printed heart models. DESIGN: We present the novel use of VR for the presurgical planning of cardiac surgery in two infants with complex CHD to demonstrate interactive real-time views of complex intra and extracardiac anatomy. RESULTS: The use of VR for cardiac presurgical planning is feasible using existing imaging data. The software was evaluated by both pediatric cardiac surgeons and pediatric cardiologists, and felt to be reliable and operated with a very short learning curve. CONCLUSIONS: VR with controller-based interactive capability allows for interactive viewing of 3D models with complex intra and extracardiac anatomy. This serves as a useful complement to traditional preoperative planning methods in terms of its potential for group based collaborative discussion, user defined illustrative views, cost-effectiveness, and facility of use.

Cardiovascular pathologies in mucopolysaccharidosis type VII (Sly Syndrome).

We present the cardiac findings from the autopsy of a 28-year-old male with mucopolysaccharidosis VII (MPS VII), also known as Sly Syndrome, whose diagnosis was confirmed by biochemical testing. The patient died a sudden cardiac death. Autopsy showed thickened and stenotic aortic valve leaflets as well as marked concentric intimal thickening of the aorta and muscular arteries. There was left ventricular hypertrophy as well as mild papillary muscle thickening and fusion. Increased colloid iron staining was seen in the small- and medium-sized arteries of the heart and at the intercalated discs. We discuss the patient's premortem echocardiographic and electrocardiographic studies. In addition, we discuss the pathogenesis of MPS VII and review previous literature on its anatomic and pathologic features.

Utility of a High-Resolution 3D MRI Sequence (3D-SPACE) for Evaluation of Congenital Heart Disease.

The purpose of this study was to evaluate the role of a high-resolution 3D dark-blood turbo spin echo sequence with variable flip angles (3D-SPACE) in evaluation of congenital heart disease. SPACE sequence was performed in 20 patients (mean age, 17.6 ± 12.6 years, range 9 months-57 years, M: 13) with either unrepaired (N = 3) or post-repair (n = 17) congenital heart disease. All scans were performed on 1.5 T Aera scanners (Siemens). Two separate observers with expertise in cardiovascular imaging scored the quality of the images for blood suppression and definition of key anatomical structures in a blinded fashion using a 5 grade scoring system. Mean of average overall quality scores for two observers was 4 ± 0.62. All overall quality scores were greater than 3. None of the studies were deemed nondiagnostic. Mean length of the SPACE acquisition time was 12.7 min (4-21 min). There was no significant correlation between image quality and duration of scans. Lack of blood suppression was the limiting factor in image quality with the most common place being ascending aorta in nine patients. However, overall blood suppression score was very good with score of 3.9 ± 0.43. There was very good overall agreement between observers in rating the image quality (85.6 % agreement, kappa 0.5, standard error 0.04, p < 0.0001). The 3D-SPACE dark-blood sequence with near-isotropic spatial resolution coupled with respiratory and cardiac gating can be feasibly performed in all age groups with diagnostic image quality in all cases in this study.

Placement of implantable cardioverter-defibrillators in paediatric and congenital heart defect patients: a pipeline for model generation and simulation prediction of optimal configurations.

There is currently no reliable way of predicting the optimal implantable cardioverter-defibrillator (ICD) placement in paediatric and congenital heart defect (CHD) patients. This study aimed to: (1) develop a new image processing pipeline for constructing patient-specific heart-torso models from clinical magnetic resonance images (MRIs); (2) use the pipeline to determine the optimal ICD configuration in a paediatric tricuspid valve atresia patient; (3) establish whether the widely used criterion of shock-induced extracellular potential (Φe) gradients ≥5 V cm(-1) in ≥95% of ventricular volume predicts defibrillation success. A biophysically detailed heart-torso model was generated from patient MRIs. Because transvenous access was impossible, three subcutaneous and three epicardial lead placement sites were identified along with five ICD scan locations. Ventricular fibrillation was induced, and defibrillation shocks were applied from 11 ICD configurations to determine defibrillation thresholds (DFTs). Two configurations with epicardial leads resulted in the lowest DFTs overall and were thus considered optimal. Three configurations shared the lowest DFT among subcutaneous lead ICDs. The Φe gradient criterion was an inadequate predictor of defibrillation success, as defibrillation failed in numerous instances even when 100% of the myocardium experienced such gradients. In conclusion, we have developed a new image processing pipeline and applied it to a CHD patient to construct the first active heart-torso model from clinical MRIs.

Tetralogy of Fallot and aortic root dilation: a long-term outlook.

Dilation of the sinus of Valsalva (SoV) has been increasingly observed after repaired tetralogy of Fallot (TOF). We estimate the prevalence of SoV dilation in adults with repaired TOF and analyze possible factors related to aortic disease. Adults with TOF [n = 109, median age 33.2 years (range 18.1 to 69.5)] evaluated at Johns Hopkins Hospital from 2001 to 2009 were reviewed in an observational retrospective cohort study. Median follow-up was 27.3 (range 0.1-48.8) years. SoV dilation was defined as >95 % confidence interval adjusted for age and body surface area (z-score > 2). The prevalence of SoV dilation was 51 % compared with that of a normal population with a mean z-score of 2.03. Maximal aortic diameters were ≥ 4 cm in 39 % (42 of 109), ≥ 4.5 cm in 21 % (23 of 109), ≥ 5 cm in 8 % (9 of 109), and ≥ 5.5 cm in 2 % (2 of 109). There was no aortic dissection or death due contributable to aortic disease. Aortic valve replacement was performed in 1.8 % and aortic root or ascending aorta (AA) replacement surgery in 2.8 % of patients. By multivariate logistic regression analysis, aortic regurgitation (AR) [odds ratio (OR) = 3.09, p = 0.005], residual ventricular septal defect (VSD) (OR = 4.14, p < 0.02), and TOF with pulmonary atresia (TOF/PA) (OR = 6.75, p = 0.03) were associated with increased odds of dilated aortic root. SoV dilation after TOF repair is common and persists with aging. AR, residual VSD, and TOF/PA are associated with increased odds of dilation. AA evaluation beyond the SoV is important. Indexed values are imperative to avoid bias on the basis of age and body surface area.

Inhaled epoprostenol therapy for pulmonary hypertension: Improves oxygenation index more consistently in neonates than in older children.

The purpose of this study was to determine the efficacy of inhaled epoprostenol for treatment of acute pulmonary hypertension (PH) in pediatric patients and to formulate a plan for a prospective, randomized study of pulmonary vasodilator therapy in this population. Inhaled epoprostenol is an effective treatment for pediatric PH. A retrospective chart review was conducted of all pediatric patients who received inhaled epoprostenol at a tertiary care hospital between October 2005 and August 2007. The study population was restricted to all patients under 18 years of age who received inhaled epoprostenol for greater than 1 hour and had available data for oxygenation index (OI) calculation. Arterial blood gas values and ventilator settings were collected immediately prior to epoprostenol initiation, and during epoprostenol therapy (as close to 12 hours after initiation as possible). Echocardiograms were reviewed during two time frames: Within 48 hours prior to therapy initiation and within 96 hours after initiation. Of the 20 patients in the study population, 13 were neonates, and the mean OI for these patients improved during epoprostenol administration (mean OI before and during therapy was 25.6±16.3 and 14.5±13.6, respectively, P=0.02). Mean OI for the seven patients greater than 30 days of age was not significantly different during treatment (mean OI before and during therapy was 29.6±15.0 and 25.6±17.8, P=0.56). Improvement in echocardiographic findings (evidence of decreased right-sided pressures or improved right ventricular function) was demonstrated in 20% of all patients. Inhaled epoprostenol is an effective therapy for the treatment of selected pediatric patients with acute PH. Neonates may benefit more consistently from this therapy than older infants and children. A randomized controlled trial is needed to discern the optimal role for inhaled prostanoids in the treatment of acute PH in childhood.

Aortic root replacement in 372 Marfan patients: evolution of operative repair over 30 years.

BACKGROUND: We reviewed the evolution of practice and late results of aortic root replacement (ARR) in Marfan syndrome patients at our institution. METHODS: A retrospective clinical review of Marfan patients undergoing ARR at our institution was performed. Follow-up data were obtained from hospital and office records and from telephone contact with patients or their physicians. RESULTS: Between September 1976 and September 2006, 372 Marfan syndrome patients underwent ARR: 269 had a Bentall composite graft, 85 had valve-sparing ARR, 16 had ARR with homografts, and 2 had ARR with porcine xenografts. In the first 24 years of the study, 85% received a Bentall graft; during the last 8 years, 61% had a valve-sparing procedure. There was no operative or hospital mortality among the 327 patients who underwent elective repair; there were 2 deaths among the 45 patients (4.4%) who underwent emergent or urgent operative repair. There were 74 late deaths (70 Bentalls, 2 homograft, and 2 valve-sparing ARRs). The most frequent causes of late death were dissection or rupture of the residual aorta (10 of 74) and arrhythmia (9 of 74). Of the 85 patients who had a valve-sparing procedure, 40 had a David II remodeling operation; there was 1 late death in this group, and 5 patients required late aortic valve replacement for aortic insufficiency. A David I reimplantation procedure using the De Paulis Valsalva graft has been used exclusively since May 2002. All 44 patients in this last group have 0 to 1+ aortic insufficiency. CONCLUSIONS: Prophylactic surgical replacement of the ascending aorta in patients with Marfan syndrome has low operative risk and can prevent aortic catastrophe in most patients. Valve-sparing procedures, particularly using the reimplantation technique with the Valsalva graft, show promise but have not yet proven as durable as the Bentall.

Assessment of Pentalogy of Cantrell using 3D Multidetector Computed Tomography.

A 7-month-old white female with Pentalogy of Cantrell was imaged using 64 slice multidetector computed tomography (MDCT) with 3D mapping to better determine the extent of cardiac, thoracic, and abdominal malformations. Complimentary to ultrasound, the use of 3D 64 slice MDCT can facilitate effective diagnosis and treatment planning in cases of Pentalogy of Cantrell.

Surgically corrected congenital heart disease: utility of 64-MDCT.

OBJECTIVE: The purpose of this article is to review the CT appearance of postoperative morphology and complications after surgical correction of congenital heart anomalies. CONCLUSION: Echocardiography is typically the initial imaging technique used for congenital heart disease; however, some thoracic regions are beyond the imaging scope of echocardiography, particularly after surgical revision. This article shows, through a series of illustrative cases, the usefulness of 64-MDCT in these patients.

Aortic root operations for Marfan syndrome: a comparison of the Bentall and valve-sparing procedures.

BACKGROUND: We compared results of the Bentall procedure with valve-sparing aortic root replacement (VSRR) for aortic root aneurysm in Marfan syndrome. METHODS: Marfan syndrome patients who had the Bentall procedure or VSRR at our institution between April 1997 and September 2006 were identified. Follow-up information was obtained from hospital charts and contact with patients or their physicians. Kaplan-Meier survival and propensity score analyses were performed. RESULTS: One hundred forty Marfan syndrome patients had either the Bentall procedure (n = 56) or VSRR (n = 84; 40 remodeling and 44 reimplantation). Bentall patients were older than VSRR patients (38 versus 29 years; p = 0.0001) and had more aortic dissections (16% versus 1%; p = 0.0012); more urgent/emergent surgery (20% versus 2%; p = 0.0008); larger preoperative sinus diameter (5.7 versus 5.1 cm; p = 0.0004); and more preoperative 3+/4+ aortic insufficiency (59% versus 10%; p < 0.0001). There were no operative deaths. Postoperatively, 9% Bentall patients (5 of 56) and 1% of VSRR patients (1 of 84) suffered thromboembolic events (p = 0.03). Two percent (1 of 56) of Bentall patients required reoperation on the aortic root versus 6% of VSRR patients (5 of 84; p = 0.40). Eight-year freedom from aortic valve replacement was 90% for VSRR patients. Eight-year survival was 90% for Bentall and 100% for VSRR patients (p = 0.01). Propensity-adjusted regression showed that the Bentall procedure did not predict mortality (p = 1.00) and did not protect from reoperation (odds ratio = 0.28; 95% confidence interval: 0.01 to 4.33; p = 0.36). CONCLUSIONS: The Bentall procedure and VSRR have similar operative results in Marfan syndrome. The procedures are distinguished by higher rates of thromboembolism among Bentall patients and higher rates of reoperation among VSRR patients. Lower late survival among Bentall patients probably reflects the preferential use of the Bentall procedure for higher risk patients.

Familial thoracic aortic dilation and bicommissural aortic valve: a prospective analysis of natural history and inheritance.

The autosomal dominant inheritance of bicommissural aortic valve (BAV) (Online Mendelian Inheritance in Man #109730) in some families is well-documented; however, the inheritance of BAV with thoracic aortic aneurysm (TAA) is less clear. Whether the aneurysm is secondary to hemodynamic perturbation related to the valve abnormality or a primary manifestation of the disorder remains controversial. Guidelines are needed regarding the follow-up and treatment of these patients and their families. Thirteen families with at least one individual with TAA and BAV (BAV/TAA) were evaluated prospectively by standard echocardiographic methods or clinical history. Affected status was determined by the presence of BAV or TAA or a history of dissection, rupture, or surgical repair. Six of 13 families had at least two family members with both BAV and TAA, often in successive generations. Informatively, all 13 families had at least one family member with TAA in the absence of BAV. Thirty-five percent (39/110) of family members had BAV/TAA or TAA, and the majority of families (11/13) had maximal dilatation above the sinotubular junction (STJ). Vascular dissection or rupture occurred in seven of 13 families and in individuals with structurally normal aortic valves. Two families had non-manifesting, obligate carriers. Three families have members with other left heart outflow tract anomalies. This study confirms autosomal dominant inheritance with incomplete penetrance for BAV/TAA in these families. Furthermore, our data suggest that the component features, BAV and TAA, are independent manifestations of a single gene defect. To avoid the risk of early death, it is essential that all first-degree relatives receive echocardiographic follow-up at regular intervals regardless of the presence or absence of a BAV. This assessment must include imaging of the aortic region above the STJ.

Progressive dilation of the ascending aorta in children with isolated bicuspid aortic valve.

Although patients with bicuspid aortic valves (BAVs) are predisposed to ascending aortic (AA) dilation, stenosis, and dissection, the development of aortic disease in children with BAVs is poorly described. The purposes of this study were to determine the rate of change of AA diameter in children with BAVs and to identify risk factors for the development of aortic dilation. The echocardiograms of 276 children aged<19 years (mean 8.5+/-5.3) with isolated BAVs were reviewed. Aortic measurements were normalized to z scores on the basis of body surface area. In a subset of 112 patients with serial examinations, aortic growth rates were calculated and risk factors for more rapid aortic growth determined. At presentation, 33 patients (12%) demonstrated marked AA dilation (z>4), and 70 (25%) were moderately abnormal (z between 2 and 4). The mean+/-SD AA diameter increased more than expected, at a rate of 0.18+/-0.30 z score per year (p<0.0001). In 61 patients with normal AA diameters on initial study, 22 (36%) had abnormal diameters, with z scores>2, at follow-up. Univariate analysis demonstrated right-noncoronary commissural fusion (p<0.02) and aortic valve gradient on initial examination (p<0.02) as significant predictors of AA growth. In multivariate analysis, however, the significance of gradient and valve morphology was diminished (p = 0.06 for both). In conclusion, the progression of AA diameter in patients with normal z scores on initial examination suggests that serial echocardiograms are required to screen for the development of significant aortic dilation.

Early surgical experience with Loeys-Dietz: a new syndrome of aggressive thoracic aortic aneurysm disease.

BACKGROUND: Loeys-Dietz syndrome (LDS) is a recently described genetic aortic aneurysm syndrome resulting from mutations in receptors for the cytokine transforming growth factor-beta. Phenotypic features include a bifid uvula, hypertelorism, cleft palate, and generalized arterial tortuosity, but risk of thoracic aortic rupture and dissection is the principle focus of management and exceeds that of most known connective tissue disorders. Our surgical experience with LDS was reviewed to assess outcomes and develop guidelines for management of this aggressive disease. METHODS: We retrospectively reviewed medical records of all LDS patients from two institutions and obtained follow-up data from medical records and patient contacts. RESULTS: Clinical criteria and genotyping were used to identify 71 patients. Before surgical intervention, 6 patients (9%) died from aneurysm rupture or dissection, which occurred in several patients with aortic diameters of less than 4.5 cm and as early as 6 months of age. Thoracic aortic aneurysm surgery was performed in 14 children and 7 adults. Operations included valve-sparing root replacement (VSRR) in 13, Bentall procedure in 5, arch replacement in 2, and VSRR with arch replacement in 1. There were no deaths at the primary operation, although 3 patients died 2, 5, and 11 years after surgery from rupture of the descending thoracic (n = 2) or abdominal aorta (n = 1). CONCLUSIONS: LDS is an aggressive aortic aneurysm disease with a propensity toward rupture and dissection at a younger age and smaller aortic diameters than in other connective tissue disorders, particularly in the ascending aorta. Early recognition of the phenotype, prophylactic intervention, and meticulous surveillance of the distal aorta and vascular tree are warranted for optimal management.

Cardiac valve assessment with MR imaging and 64-section multi-detector row CT.

A variety of noninvasive techniques are available to assess cardiac valve morphologic features and function, with echocardiography currently being the most widely used modality for this purpose. Technical advances in electrocardiographically gated multi-detector row computed tomography (CT) and magnetic resonance (MR) imaging allow the noninvasive visualization of the cardiac valves. At present, 64-section multi-detector row CT and MR imaging are commonly being used for comprehensive examination of the heart. Information about the cardiac valves is routinely provided by MR imaging of cardiac function or coronary CT angiography. Thus, the interpreting physician may have additional information available that can aid in making the diagnosis. Supplemental movie clips are available at http://radiographics.rsnajnls.org/cgi/content/full/26/6/1769/DC1.

Penetrance of mutations in plakophilin-2 among families with arrhythmogenic right ventricular dysplasia/cardiomyopathy.

OBJECTIVES: The purpose of our study was to characterize the penetrance of PKP2 mutations among family members of people with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and to examine clinical features and predictors of disease among PKP2 mutation carriers. BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy is an inherited cardiomyopathy characterized by fatty-fibrous myocardial replacement of the right ventricle, ventricular arrhythmias, and right ventricular dysfunction. Mutations in PKP2, the gene encoding plakophilin-2, are found in 11% to 43% of ARVD/C probands. METHODS: The study population was composed of 64 individuals in 9 families with an ARVD/C proband previously shown to carry a pathogenic PKP2 mutation. The diagnosis of ARVD/C was established based on task force criteria (TFC) set by the European Society of Cardiology. RESULTS: In addition to the probands, PKP2 mutations were present in 52% of relatives screened. Forty-nine percent of PKP2 mutation carriers met TFC. Among mutation carriers who did not meet full TFC, 50% met at least some TFC criteria besides family history. Pedigrees showed wide intra-familial variability, ranging from severe disease with early death to individuals who were completely asymptomatic late in life. Male PKP2 mutation carriers were more likely to have structural and conduction abnormalities as determined by imaging studies, signal-averaged electrocardiography, and 24-h ambulatory electrocardiography (p < 0.05). CONCLUSIONS: PKP2 mutations in a group of North American families with ARVD/C have both reduced penetrance and variable expressivity. Gender may have an influence on penetrance of PKP2 mutations, with male mutation carriers more likely to develop specific phenotypic manifestations of this disease.

Recessive arrhythmogenic right ventricular dysplasia due to novel cryptic splice mutation in PKP2.

Arrhythmogenic right ventricular dysplasia (ARVD) is a genetic disorder resulting in fibro-fatty replacement of right ventricular myocytes and consequent ventricular arrhythmias. Heterozygous mutations in PKP2 encoding plakophilin-2 have previously been reported to cause dominant ARVD with reduced penetrance. We report the first case of recessive ARVD caused by mutations in PKP2. Candidate gene analysis in a typical proband with this disorder identified a novel homozygous mutation in PKP2 (c.[2484C>T]+[2484C>T]), which is predicted to be translationally silent (p.Gly828). Analysis of the proband's mRNA, however, shows that this mutation causes predominantly cryptic splicing, with a 7-nucleotide deletion in exon 12. The ensuing frame shift disrupts the last 54 amino acids of plakophilin-2 and extends the open reading frame by 145 nucleotides (48 amino acids) into the 3' untranslated region. Haplotype analysis demonstrates the absence of remote consanguinity. Heterozygous family members produce approximately 60% of properly spliced PKP2 and do not have manifestations of ARVD. Further analysis of PKP2 mRNA sequence revealed two additional alternatively spliced transcripts. The possibility of cryptic or alternative splicing should be considered with identification of apparently synonymous nucleotide substitutions in this gene.

Valve-sparing aortic root replacement: early experience with the De Paulis Valsalva graft in 51 patients.

BACKGROUND: Valve-sparing aortic root replacement for treatment of aortic sinus disease avoids the problems of prosthetic valves, but some patients suffer late valve incompetence as a result of leaflet distortion or annular dilatation. The reimplantation technique using the De Paulis Valsalva graft might improve late results of valve-sparing aortic root replacement by maintaining annular stability and re-creating sinuses that minimize leaflet stress. METHODS: Retrospective review was conducted of all patients at our institution who underwent valve-sparing aortic root replacement using the Valsalva graft. Clinical data were obtained from hospital and clinic charts and patient contacts; echocardiograms were analyzed for aortic root dimensions and valve function. RESULTS: Between May 2002 and June 2005, 51 patients underwent valve-sparing aortic root replacement using the reimplantation technique with the Valsalva graft. Mean age was 33 +/- 15 years; 22% (11 of 51) were children, and 80% (41 of 51) were male. Primary indication for surgery was root aneurysm in all patients. Preoperative mean root diameter was 5.0 +/- 0.5 cm. Marfan syndrome was present in 67% (34 of 51), and 10% (5 of 51) had the newly described Loeys-Dietz syndrome. There were no operative or late deaths, and no patient required reoperation for bleeding. At mean follow-up of 1.8 years, there were no episodes of endocarditis or thromboembolism. Echocardiograms showed stability of the annulus and root dimensions on follow-up. No patient had more than 0 to 1+ aortic insufficiency or progression of aortic insufficiency. All were in New York Heart Association class I. CONCLUSIONS: Valve-sparing aortic root replacement using the Valsalva graft and reimplantation technique has excellent early results. Preservation of valve competence is encouraging, but long-term results will determine whether the anatomic design of this aortic root prosthesis is superior for preservation of valve integrity.