David M. Harrild

Pulmonary Valve Replacement in Tetralogy of Fallot Impact on Survival and Ventricular Tachycardia

Background— Pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (TOF) reduces pulmonary regurgitation and decreases right ventricular (RV) dilation, but its long-term impact on ventricular tachycardia (VT) and mortality is unknown. This study aimed to determine the incidence of death and VT in TOF after PVR and to test the hypothesis that PVR leads to improvement in these outcomes. Methods and Results— A total of 98 patients with TOF and late PVR for RV dilation were identified. Matched control subjects were identified for 77 of these patients; control subjects had TOF with RV dilation but no PVR. Matching was done by age (±2 years) and baseline QRS duration (±30 ms). No significant differences were found in age, QRS duration, type or decade of initial repair, age at TOF repair, or presence of pre-PVR VT between the 2 groups; limited echocardiographic and magnetic resonance imaging data showed no difference in left ventricular function but more RV dilation among PVR patients than control subjects. In the PVR group, 13 events occurred over 272 patient-years. No significant change in QRS duration was seen for any group. Overall 5- and 10-year freedom from death, VT, or both was 80% and 41%, respectively. In the matched comparison, no significant differences were seen in VT, death, or combined VT and/or death (P=0.32, P=0.06 [nearly favoring controls], and P=0.21). Conclusions— This cohort experienced either VT or death every 20 patient-years. In a matched comparison with a similar TOF group, late PVR for symptomatic pulmonary regurgitation/RV dilation did not reduce the incidence of VT or death.

Long-Term Pulmonary Regurgitation Following Balloon Valvuloplasty for Pulmonary Stenosis: Risk Factors and Relationship to Exercise Capacity and Ventricular Volume and Function

OBJECTIVES This study sought to examine the prevalence and predictors of pulmonary regurgitation (PR) following balloon dilation (BD) for pulmonary stenosis (PS) and to investigate its impact on ventricular volume and function, and exercise tolerance. BACKGROUND Balloon pulmonary valvuloplasty relieves PS but can cause late PR. The sequelae of isolated PR are not well understood. METHODS Patients were at least 7 years of age and 5 years removed from BD, and had no other form of congenital heart disease or significant residual PS. Cardiac magnetic resonance imaging and exercise testing were performed prospectively to quantify PR fraction, ventricular volumes and function, and exercise capacity. RESULTS Forty-one patients underwent testing a median of 13.1 years after BD. The median PR fraction was 10%; 14 patients (34%) had PR fraction >15%; 7 (17%) had PR >30%. PR fraction was associated with age at dilation (ln-transformed, R = -0.47, p = 0.002) and balloon:annulus ratio (R = 0.57, p < 0.001). The mean right ventricular (RV) end-diastolic volume z-score was 1.8 +/- 1.9; RV dilation (z-score > or =2) was present in 14/35 patients (40%). PR fraction correlated closely with indexed RV end-diastolic volume (R = 0.79, p < 0.001) and modestly with RV ejection fraction (R = 0.50, p < 0.001). Overall, peak oxygen consumption (Vo(2)) (% predicted) was below average (92 +/- 17%, p = 0.006). Patients with PR fraction >15% had significantly lower peak Vo(2) than those with less PR (85 +/- 17% vs. 96 +/- 16%, p = 0.03). CONCLUSIONS Mild PR and RV dilation are common in the long term following BD. A PR fraction >15% is associated with lower peak Vo(2), suggesting that isolated PR and consequent RV dilation are related to impaired exercise cardiopulmonary function.

A finite volume model of cardiac propagation

This paper describes a two-dimensional cardiac propagation model based on the finite volume method (FVM). This technique, originally derived and applied within the field of computational fluid dynamics, is well suited to the investigation of conduction in cardiac electrophysiology Specifically, the FVM permits the consideration of propagation in a realistic structure, subject to arbitrary fiber orientations and regionally defined properties. In this application of the FVM, an arbitrarily shaped domain is decomposed into a set of constitutive quadrilaterals. Calculations are performed in a computational space, in which the quadrilaterals are all represented simply as squares. Results are related to their physical-space equivalents by means of a transformation matrix. The method is applied to a number of cases. First, large-scale propagation is considered, in which a magnetic resonance-imaged cardiac cross-section serves as the governing geometry. Next, conduction is examined in the presence of an isthmus formed by the microvasculature in a slice of papillary muscle tissue. Under ischemic conditions, the safety factor for propagation is seen to be related to orientation of the fibers within the isthmus. Finally, conduction is studied in the presence of an inexcitable obstacle and a curved fibe field. This example illustrates the dramatic influence of the complex orientation of the fibers on the resulting activation pattern. The FVM provides a means of accurately modeling the cardiac structure and can help bridge the gap between computation and experiment in cardiac electrophysiology.

Relation of Left Ventricular Dyssynchrony Measured by Cardiac Magnetic Resonance Tissue Tracking in Repaired Tetralogy of Fallot to Ventricular Tachycardia and Death

The impact of left ventricular (LV) dyssynchrony on clinical outcomes in patients with tetralogy of Fallot (TOF) is unknown. The aim of this study was to test the hypothesis that LV dyssynchrony assessed by cardiac magnetic resonance (CMR)-derived tissue tracking in patients with repaired TOF is associated with ventricular tachycardia (VT) and death. Included patients had repaired TOF and CMR data from 2000 and 2008. Patients (n = 13) had histories of death or sustained VT. Control subjects (n = 26), with no death or VT, were matched by age at CMR and type of last surgical procedure. Demographic, clinical, and electrocardiographic data were recorded. CMR short-axis cine data were analyzed by tracking the motion of the endocardial border using commercial software. LV dyssynchrony was quantified as the maximum difference in time to peak radial displacement, circumferential strain, and radial strain among the 6 ventricular segments and the standard deviation of the times to peak value. There were no differences between groups in clinical, electrocardiographic, or demographic characteristics. Among CMR parameters, right ventricular volumes were higher and ejection fractions lower in the patient group. Indexes of LV dyssynchrony were higher in the patient group (e.g., maximum time difference of circumferential strain 94 vs 46 ms, p <0.001; standard deviation of circumferential strain 37.8 vs 20.3 ms, p <0.01). In a multivariate model including LV synchrony variables, the best outcome discriminator was maximum time difference to peak circumferential strain (p <0.01). In conclusion, tissue tracking applied to CMR images identifies indexes of LV synchrony associated with death and VT in patients with repaired TOF.

Circumferential and longitudinal ventricular strain in the normal human fetus.

BACKGROUND Echocardiography with speckle tracking is a novel, angle-independent technique for assessing global and regional cardiac function. Normal data on longitudinal strain have been reported for human fetuses. The aim of this study was to define circumferential left ventricular (LV) strain in a normal fetal population. METHODS Singleton fetuses between 17 and 42 weeks in gestational age with no adverse maternal health issues or fetal abnormalities were studied. Regional and averaged cardiac strain were measured using syngo Velocity Vector Imaging software. RESULTS Data from 81 fetuses were analyzed (mean gestational age, 29.2 ± 5.7 weeks). Overall, average midventricular circumferential strain was 18.7 ± 3.3%, LV longitudinal strain was 15.2 ± 2.7%, and right ventricular longitudinal strain was 16.0 ± 3.3%, with no correlation with gestational age. CONCLUSION This is the first study to report normal fetal LV circumferential strain. These data may be useful as a reference for assessing fetal cardiac function. The retrospective study design and relatively low frame rates used in this study were important limitations.

Longitudinal Exercise Capacity of Patients With Repaired Tetralogy of Fallot

Patients with repaired tetralogy of Fallot have a reduced percentage of predicted peak oxygen consumption (VO(2)) and percentage of oxygen pulse (O(2)P%) compared to healthy controls. Because data regarding the progression of exercise intolerance in these patients is limited, we sought to analyze the serial exercise data from patients with Tetralogy of Fallot to quantify the changes in their exercise capacity over time and to identify associations with clinical and cardiac magnetic resonance imaging variables. The data from cardiopulmonary exercise tests (CPXs) from 2002 to 2010 for patients with repaired tetralogy of Fallot with ≥2 CPXs separated by ≥12 months were analyzed. Tests occurring after interventional catheterization or surgery were excluded. A total of 70 patients had 179 CPXs. They had a median age at the initial study of 23.6 years and an interval between the first and last CPX of 2.8 years. At the initial CPX, the peak VO(2) was 27.6 ± 8.8 ml/kg/min (78 ± 19% of predicted), and the peak O(2)P% was 89 ± 22% of predicted. At the most recent study, the peak VO(2) averaged 25.0 ± 7.4 ml/kg/min (73 ± 16% of predicted), and the peak O(2)P% averaged 83 ± 20% (p <0.01) for each versus the initial CPX. The decrease in the peak VO(2) was strongly associated with a decrease in O(2)P% and an increase (worsening) in the slope of the minute ventilation-versus-carbon dioxide production relation. Changes in the peak VO(2) did not correlate with concomitant changes in any other CPX variable. The rate of decrease was not related to a history of shunt palliation, age at CPX, or any other baseline clinical parameter, including cardiac magnetic resonance measurements. In conclusion, the exercise capacity of patients with repaired tetralogy of Fallot tends to decrease over time. This deterioration is variable and unpredictable and is primarily related to a decrease in the forward stroke volume at peak exercise.

Relation of Biventricular Strain and Dyssynchrony in Repaired Tetralogy of Fallot Measured by Cardiac Magnetic Resonance to Death and Sustained Ventricular Tachycardia

Ventricular strain and dyssynchrony can be measured in patients with repaired tetralogy of Fallot (TOF), but their effect on clinical outcomes is poorly understood. The purpose of this study was to investigate if ventricular strain and dyssynchrony measured by cardiac magnetic resonance feature tracking are associated with death and sustained ventricular tachycardia. Patients with TOF who died or had ventricular tachycardia (TOF case, n = 16) were compared with age-matched patients with TOF with no adverse outcome (TOF control, n = 32). For each patient, midventricular short-axis and 4-chamber cine steady-state free precession images were analyzed using cardiac magnetic resonance feature-tracking software. Peak left ventricular (LV) and right ventricular (RV) global circumferential and longitudinal strain and indexes of dyssynchrony were compared between groups. Compared with the TOF control group, median strain values were significantly lower for the TOF case group for both the LV (circumferential: 17% vs 23%, p = 0.003; longitudinal: 13% vs 18%, p <0.001) and the RV (circumferential: 10% vs 16%, p = 0.001; longitudinal: 11% vs 18%, p <0.001). In a multivariate model including strain and dyssynchrony parameters, RV and LV longitudinal strain were strongly associated with the adverse outcome (p = 0.003 and 0.04, respectively; area under the curve = 0.92). No differences in ventricular dyssynchrony were identified between the groups. In conclusion, patients with TOF in this cohort who experienced adverse outcomes had lower values of all strain parameters than those who did not, and impaired longitudinal strain of both ventricles was strongly associated with adverse clinical outcomes.

Left ventricular function and geometry in fetuses with severe tricuspid regurgitation

Neonatal congenital tricuspid valve (TV) dysplasia and/or displacement (Ebsteins malformation) with severe tricuspid regurgitation (TR) is a challenging condition in which outcomes are frequently poor. Little is known about left ventricular (LV) function during the perinatal period in patients with congenital TV disease. The objective of this study was to evaluate LV function in fetuses with congenital TV anomalies associated with significant TR.

Impact of Transcatheter Pulmonary Valve Replacement on Biventricular Strain and Synchrony Assessed by Cardiac Magnetic Resonance Feature Tracking

Background—Transcatheter pulmonary valve (TPV) replacement is an emerging therapy intended to restore pulmonary valve function in patients with right ventricular outflow tract conduit dysfunction; the impact of this technique on ventricular strain and synchrony is not known. Methods and Results—Cardiac magnetic resonance and ECG data acquired at 1 center as part of the US Melody TPV trial were analyzed. Biventricular strain and mechanical synchrony measurements were made based on short-axis and 4-chamber steady-state free precession images using feature tracking software. Post- versus pre-TPV replacement findings were compared for all patients (n=31) and subgroups with predominant pulmonary regurgitation (n=13) or stenosis (n=18). Most patients had tetralogy of Fallot (18/31). After TPV replacement, left ventricular (LV) circumferential strain increased for the whole cohort (P<0.001) and both subgroups (pulmonary regurgitation P=0.01; pulmonary stenosis P=0.02). LV longitudinal strain increased for the whole cohort (P=0.02) and pulmonary regurgitation subgroup (P=0.05); circumferential right ventricular strain increased for the pulmonary stenosis group only (P=0.05). LV longitudinal synchrony improved significantly in the pulmonary regurgitation group (maximum wall delay P=0.03; cross-correlation delay P=0.01). Electric measures of synchrony did not improve. Conclusions—In patients with right ventricular outflow tract conduit dysfunction, TPV replacement is associated with improved global LV strain, as well as improved right ventricular strain and LV synchrony in subgroups. Given the associations between strain and synchrony and clinical outcomes, these findings support potential long-term benefits of TPV replacement.

Autologous mitochondrial transplantation for dysfunction after ischemia-reperfusion injury

From the Departments of Cardiac Surgery and Cardiology, Boston Children’s Hospital, Boston, Mass. Supported by The Richard A. and Susan F. Smith Foundation, President’s Innovation Award, Boston Children’s Hospital; Michael B. Klein and Family; the Sidman Family Foundation; the Bulens/Capozzi Foundation; and the Kenneth C. Griffin Charitable Research Fund. The authors attest that they had full freedom to explore the data and analyze the results independently of any sponsor and that they had sole authority to make the final decision to submit the material for publication. Disclosures: J.D.M. and P.J.dN. have patents pending for the isolation and usage of mitochondria have patents pending for the isolation and usage of mitochondria. All other authors have nothing to disclose with regard to commercial support. Received for publication Oct 12, 2016; revisions received Dec 23, 2016; accepted for publication Feb 8, 2017; available ahead of print March 7, 2017. Address for reprints: Sitaram M. Emani, MD, Boston Children’s Hospital, 300 Longwood Ave, Bader 273, Boston, MA 02115 (E-mail: Sitaram.Emani@cardio.chboston.org). J Thorac Cardiovasc Surg 2017;154:286-9 0022-5223/