Effect of voxelotor on cardiopulmonary testing in youths with sickle cell anemia in a pilot study.

BACKGROUND: Individuals with sickle cell anemia (SCA) exhibit decreased exercise capacity. Anemia limits oxygen-carrying capacity and affects cardiopulmonary fitness. The drug voxelotor raises hemoglobin in SCA. We hypothesized that voxelotor improves exercise capacity in youths with SCA. METHODS: In a single-center, open-label, single-arm, longitudinal interventional pilot study (NCT04581356), SCA patients aged 12 and older, stably maintained on hydroxyurea, were treated with 1500 mg voxelotor daily, and performed cardiopulmonary exercise testing before (CPET#1) and after voxelotor (CPET#2). A modified Bruce Protocol was performed on a motorized treadmill, and breath-by-breath gas exchange data were collected. Peak oxygen consumption (peak VO2 ), anaerobic threshold, O2 pulse, VE/VCO2 slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO2 . Hematologic parameters were measured before each CPET. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected. RESULTS: Ten hemoglobin SS patients aged 12-24 completed the study. All demonstrated expected hemoglobin rise, with average +1.6 g/dL (p = .003) and P50 left shift of average -11 mmHg (p < .0001) with decreased oxygen off-loading at low pO2 . The change in % predicted peak VO2 from CPET#1 to CPET#2 ranged from -12.8% to +11.3%, with significant improvement of more than 5% in one subject, more than 5% decrease in five subjects, and insignificant change of less than 5% in four subjects. All 10 CGIC and seven of 10 PGIC responses were positive. CONCLUSION: In a plot study of 10 youths with SCA, voxelotor treatment did not improve peak VO2 in 9 out of 10 patients.

Changes in hemodynamic parameters and cerebral saturation during supraventricular tachycardia.

Induced supraventricular tachycardia (SVT) during electrophysiology studies (EPS) can be associated with hemodynamic changes. Traditionally, invasive arterial blood pressure has been used for continuous monitoring of these changes. This prospective study evaluated the efficacy of near-infrared spectroscopy (NIRS) monitoring during SVT. The use of NIRS has expanded with evidence of its accuracy and benefit in detecting cerebral hypoperfusion. This study aimed first to determine the hemodynamic changes associated with electrophysiology testing for SVT and second to determine whether the hemodynamic changes are associated with similar changes in the cerebral saturation as determined by NIRS. The study enrolled 30 patients 5-20 years of age with a history of SVT who underwent an EPS. The demographic data included age, gender, weight, height, and type of SVT. Hemodynamic data (invasive blood pressure and heart rate), NIRS, bispectral index (BIS), end-tidal carbon dioxide, and pulse oximetry were collected before and during three episodes of induced SVT. The linear correlation coefficient (r) was measured to calculate the relationship of the changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) to the changes in NIRS values during the SVT episodes. Data from 22 patients were collected. The induction of SVT was associated mainly with a change in SBP and a less prominent change in DBP and MAP from baseline. The changes in hemodynamic status were associated with minimal changes in cerebral saturations, as evidenced by an average absolute change in NIRS of <1 from baseline value. The changes in hemodynamics were correlated linearly with cerebral saturation. Changes in SBP, DBP, and MAP were correlated positively with changes in NIRS, as denoted by (r) values of 0.52, 0.57, and 0.67 respectively, and a P value less than 0.05 for all three association tests. Induction of SVT during electrophysiology testing is associated with hemodynamic changes, mainly in SBP. In this study, these hemodynamic changes resulted in a minimal decrease in cerebral perfusion, as evidenced by minimal changes in the cerebral saturation measured by NIRS (0.7% from baseline). Although the changes in the cerebral saturation were minimal, these changes were linearly correlated with the changes in the hemodynamics. This study is the first to demonstrate the possible application of NIRS monitoring during EPS and to document that despite changes in the hemodynamic status, the changes in cerebral oxygenation are minimal, thereby confirming the safety of EPS for SVT.

Ruptured myocardial abscess causing left ventricle to pulmonary artery communication in an infant with community-associated methicillin-resistant Staphylococcus aureus endocarditis.

Myocardial abscess perforation is an extremely rare complication of infective endocarditis. We present a case of a 12-month-old infant who developed community-associated methicillin-resistant Staphylococcus aureus bacteremia after an incision and drainage of a skin abscess. He subsequently developed septic emboli to the brain and lungs, and a myocardial cavity in the outlet portion of the interventricular septum. The cavity ruptured 4 days after diagnosis and created a left ventricle to pulmonary artery fistulous communication. The patient died secondary to embolic complications to the brain. We are not aware of any other cases of myocardial abscess rupture in this location of the heart, in a patient of this age, or due to infection with community-associated methicillin-resistant S aureus .

Echocardiographic assessment of atrial properties in single ventricles vs. normal controls.

INTRODUCTION: Atrial function is increasingly being recognized as a significant factor in overall cardiac function in adults. Limited studies evaluating atrial properties exist in the pediatric congenital heart disease population. The goal of this study was to evaluate atrial properties in patients with single ventricle physiology after Fontan completion and compare these values with normal control patients. METHODS: Echocardiograms were performed in patients with single ventricular physiology and in control patients. Tissue Doppler and blood flow measurements were obtained. Atrial fraction and atrial electromechanical values were calculated. Differences were assessed with one-way analysis of variance. Post hoc comparisons were performed with Tukey adjustment. P < .05 was considered significant. RESULTS: No significant difference was present in age or heart rate between single ventricle and control patients. The single right ventricle tricuspid valve A wave (52.6 ± 14.5 vs. 36.7 ± 10.4 cm/s) and atrial fraction (39.2 ± 6.2 vs. 32.7 ± 7.7%) were significantly higher, and the E/A ratio (1.4 + 0.3 vs. 1.8 + 0.4), tricuspid valve E/A velocity-time integral (1.6 + 0.4 vs. 2.2 + 0.7 cm), and late diastolic annular value (5.3 + 1.5 vs. 8.7 + 1.4 cm/s) were significantly lower compared with the controls. The single left ventricle late diastolic annular velocity (4.2 + 1.0 vs. 6.7 + 1.3 cm/s) was significantly lower and atrial fraction was significantly higher compared with the controls (37.7 ± 12.5 vs. 29.8 ± 4.3%). There were no significant differences in atrial electromechanical measurements between groups, but the single right ventricle patients tended to have increased atrial dyssynchrony compared with controls. CONCLUSIONS: Patients with single ventricle physiology after Fontan completion have differences in atrial properties when compared with normal controls. These differences may have important implications in their long-term outcomes. Further studies are necessary to determine the clinical significance of these findings.

Two-dimensional speckle strain and dyssynchrony in single left ventricles vs. normal left ventricles.

BACKGROUND: Patients with single left ventricle (LV) physiology maybe at increased risk for myocardial dysfunction and mechanical dyssynchrony. Newer echocardiographic modalities may be able to better quantitate LV function in this unique population. Our objective was to use 2D-speckle analysis of strain and strain rate to quantify systolic function and dyssynchrony in single LV post-Fontan patients and compare them to control LV patients. METHODS: Patients with single LV status post-Fontan procedure and patients with normal biventricular anatomy were studied. Two-dimensional speckle echocardiography was used to measure strain, strain rate, time to peak, and longitudinal displacement in a six-segment model of the LV. Independent t-tests were used to compare group means. RESULTS: Twelve patients with single LV physiology and thirteen control patients were studied. There was no significant difference in ages for the single LV patients vs. control patients (7.1 + 2.8 years vs. 5.7 + 1.8 years). Single LV strain values were significantly lower in four of the six segments compared with control LV (mid interventricular septal [IVS]: -19.3 + 6.4% vs. -23.8 + 3.5%, apical IVS: -20.8 + 5.4% vs. -27.4 + 4.7%, basal LV: -20.6 + 6.6% vs. -25.8 + 3.4%, and apical LV: -21.0 + 6.2% vs. -26.1 + 4.3%). Longitudinal displacement was lower for all three segments of the IVS for the single LV vs. control LV. Modified Yu index for strain and strain rate time to peak was longer in the single LV patients vs. controls (51.2 + 18.2 ms vs. 27.9 + 8.0 ms and 90.2 + 24.2 ms vs. 52.5 + 23.7 ms, respectively). CONCLUSION: Significant differences in strain analysis between single LV patients vs. control patients with normal biventricular physiology exist at a relatively young age. Future studies are needed to determine the significance of these differences.

Differences in tissue Doppler imaging between single ventricles after the fontan operation and normal controls.

Tissue Doppler imaging measurements could be used to quantitate ventricular function in patients with systemic single ventricles. The objective of the present study was to measure the tissue doppler imaging-derived indexes of function and dyssynchrony in patients with single ventricular physiology and compare these values with those from control patients. Echocardiograms were performed in patients with single left or right ventricular physiology and control patients. Measurements were made of the free walls at the level of the atrioventricular annulus. Differences were assessed with one-way analysis of variance. Post hoc comparisons were performed with a Tukey adjustment. No significant difference was present in age among the control (5.75 +/- 1.73 years, n = 16), single left ventricle (7.07 +/- 2.81 years, n = 12), or single right ventricle (6.25 +/- 2.2 years, n = 14) groups. The single right ventricular free wall peak systolic annular, peak early diastolic annular, and peak late diastolic annular velocities were significantly lower and the myocardial performance index and interval to mechanical activation greater compared to the controls. The single left ventricular free wall peak systolic annular, peak early diastolic annular, and peak late diastolic annular velocities were also significantly lower and the myocardial performance index and interval to mechanical activation greater compared to controls. In conclusion, significant decreases in systolic and diastolic function, as well as differences in dyssynchrony, using tissue Doppler imaging exist in patients with single ventricular physiology compared to control patients.

Two-dimensional speckle strain and dyssynchrony in single right ventricles versus normal right ventricles.

BACKGROUND: Patients with single-right ventricle (RV) physiology are at increased risk for myocardial dysfunction and mechanical dyssynchrony. Newer echocardiographic modalities may be better able to quantitate right ventricular function in this unique population. The aim of this study was to use two-dimensional speckle analysis of strain and strain rate to quantify systolic function and dyssynchrony in single-RV post-Fontan patients and compare them with values for controls. METHODS: Patients with single RV who underwent Fontan palliation and patients with normal biventricular anatomy were studied. Two-dimensional speckle echocardiography was used to measure strain, strain rate, time to peak, and longitudinal displacement in a 6-segment model of the RV. Independent t tests were used to compare group means. P values < .05 were considered significant. RESULTS: Thirteen patients were studied in each group. There was no significant difference in age between single-RV patients and controls (6.60 +/- 2.07 vs 5.75 +/- 1.83 years, respectively). Single-RV strain values were significantly lower in all 6 segments compared with values in controls (basal interventricular septum [IVS], -14.28 +/- 7.78% vs -22.00 +/- 2.36%; mid IVS, -17.70 +/- 4.54% vs -22.99 +/- 2.71%; apical IVS, -19.46 +/- 4.97% vs -25.42 +/- 4.06%; basal RV, -22.40 +/- 5.7% vs -41.42 +/- 5.42%; mid RV, -21.20 +/- 3.21% vs -39.67 +/- 6.04%; apical RV, -20.70 +/- 4.90% vs -33.68 +/- 3.90%). Systolic strain rate and longitudinal displacement were also lower in the free wall and apical IVS in single-RV patients compared with controls. The modified Yu index for strain time to peak was longer in the single-RV patients (43.16 +/- 13.63 vs 21.72 +/- 7.25 ms). CONCLUSION: Significant differences in strain analysis between single-RV patients and patients with biventricular physiology exist at a relatively young age. Future studies are needed to determine the clinical significance of these differences.