Clinically Suspected Myocarditis Temporally Related to COVID-19 Vaccination in Adolescents and Young Adults: Suspected Myocarditis After COVID-19 Vaccination.

BACKGROUND: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth. METHODS: We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings. Myocarditis cases were classified as confirmed or probable on the basis of the Centers for Disease Control and Prevention definitions. RESULTS: We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1-20.3; interquartile range [IQR], 14.5-17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0-22; IQR, 1-3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0-10; IQR, 2-3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50-15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25-1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction <55% on echocardiogram. Of 97 patients who underwent cardiac MRI at a median 5 days (range, 0-88; IQR, 3-17) from symptom onset, 75 (77.3%) had abnormal findings: 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria. Among 26 patients with left ventricular ejection fraction <55% on echocardiogram, all with follow-up had normalized function (n=25). CONCLUSIONS: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons <21 years have a mild clinical course with rapid resolution of symptoms. Abnormal findings on cardiac MRI were frequent. Future studies should evaluate risk factors, mechanisms, and long-term outcomes.

Cardiac Surgery in Patients With Trisomy 13 and 18: An Analysis of The Society of Thoracic Surgeons Congenital Heart Surgery Database.

Background Congenital heart disease is common in patients with Trisomy 13 (T13) and Trisomy 18 (T18), but offering cardiac surgery to these patients has been controversial. We describe the landscape of surgical management across the United States, perioperative risk factors, and surgical outcomes in patients with T13 and T18. Methods and Results Patients in the Society of Thoracic Surgeons Congenital Heart Surgery Database with T13 and T18 who underwent cardiac surgery (2010-2017) were included. There were 343 operations (T13: n=73 and T18: n=270) performed on 304 patients. Among 125 hospitals, 87 (70%) performed at least 1 operation and 26 centers (30%) performed ≥5 T13/T18 operations. Operations spanned the full spectrum of complexity with 29% (98/343) being in the highest categories of estimated risk. The operative mortality rate was 15%, with a 56% complication rate. Preoperative mechanical ventilation was associated with an odds ratio of mortality >8 for both patients with T13 and T18 (both P<0.012) while presence of a gastrostomy tube (odds ratio, 0.3; P=0.03) or prior cardiac surgery (odds ratio, 0.2; P=0.02) was associated with better survival in patients with T18 but not patients with T13. Conclusions Data from this nationally representative sample indicate that most centers offer surgical intervention for both patients with T13 and T18, even in highly complex patients. However, the overall mortality rate was high in this select patient cohort. The association of preoperative mechanical ventilation with mortality suggests that this subset of patients with T13 and T18 should perhaps not be considered surgical candidates. This information is valuable to clinicians and families for counseling and deciding what interventions to offer.

Echocardiographic factors discriminating biventricular versus univentricular approach in the foetus with borderline left ventricle.

BACKGROUND: The term "borderline left ventricle" describes a small left heart that may be inadequate to provide systemic cardiac output and implies the potential need for a single-ventricle palliation. The aim of this study was to identify foetal echocardiographic features that help discriminate which infants will undergo single-ventricle palliation versus biventricular repair to aid in prenatal counselling. METHODS: The foetal database at our institution was searched to identify all foetuses with borderline left ventricle, as determined subjectively by a foetal cardiologist, from 2000 to 2011. The foetal images were retrospectively analysed for morphologic and physiologic features to determine which best predicted the postnatal surgical choice. RESULTS: Of 39 foetuses identified with borderline left ventricle, 15 were planned for a univentricular approach, and 24 were planned for a biventricular approach. There were significant differences between the two outcome groups in the Z-scores of the mitral valve annulus, left ventricular end-diastolic dimension, aortic valve annulus, and ascending aorta diameter (p<0.05). With respect to discriminating univentricular outcomes, cut-offs of mitral valve Z-score ⩽-1.9 and tricuspid:mitral valve ratio ⩾1.5 were extremely sensitive (100%), whereas a right:left ventricular end-diastolic dimension ratio ⩾2.1 provided the highest specificity (95.8%). CONCLUSION: In foetuses with borderline left ventricle, a mitral valve Z-score ⩾-1.9 or a tricuspid:mitral valve ratio ⩽1.5 suggests a high probability of biventricular repair, whereas a right:left ventricular end-diastolic dimension ratio ⩾2.1 confers a likelihood of single-ventricle palliation.

Screening for cardiac dysfunction in anthracycline-exposed childhood cancer survivors.

PURPOSE: To examine the utility and reliability of obtaining early echocardiographic measurements of left ventricular (LV) remodeling as well as blood biomarkers of cardiac injury in asymptomatic childhood cancer survivors at risk for LV dysfunction and congestive heart failure due to past exposure to anthracycline chemotherapy. EXPERIMENTAL DESIGN: Using a cross-sectional design, anthracycline-exposed childhood cancer survivors with preserved ejection fraction (EF; ≥50%) were evaluated using early echocardiographic indices and blood biomarkers of LV dysfunction. Survivors treated with ≥300 mg/m(2) anthracyclines [high risk (HR): n = 100] were compared with those treated with <300 mg/m(2) anthracyclines [low risk (LR): n = 50] and matched healthy controls (HC: n = 50). All echocardiograms were interpreted by an institutional cardiologist and a study cardiologist blinded to risk status. RESULTS: Time from diagnosis was comparable for HR (12.0 years) and LR (13.2 years, P = 0.8) survivors. Echocardiograms: HR had lower LV thickness-dimension ratio (Z-score: HR: -0.62, LR: -0.03, HC: -0.02; P < 0.001), increased LV wall stress (HR: 66.7 g/cm(2), LR: 56.6 g/cm(2), HC: 54.2 g/cm(2); P < 0.01), and higher myocardial performance index (HR: 0.51, LR: 0.46, HC: 0.46; P < 0.01). Interobserver correlation (clinical/blinded reading) for all echocardiographic indices was excellent (range: R = 0.76-0.97, P < 0.001). Blood biomarkers: With the exception of NT-proBNP (r = 0.28, P < 0.01), there was no correlation between blood biomarkers (B-type natriuretic peptide, Troponin-T, ST-2, Galectin-3) and LV dysfunction. CONCLUSION: Childhood cancer survivors with preserved EF 10+ years from anthracycline exposure had dose-dependent changes in echocardiographic markers of LV dysfunction.

Carnitine and cardiac dysfunction in childhood cancer survivors treated with anthracyclines.

Childhood cancer survivors are at high risk of developing congestive heart failure (CHF) compared with the general population, and there is a dose-dependent increase in CHF risk by anthracycline dose. The mechanism by which this occurs has not been fully elucidated. Metabolomics, the comprehensive profile of small-molecule metabolites, has the potential to provide insight into the pathogenesis of disease states and discover diagnostic markers for therapeutic targets. We performed echocardiographic testing and blood plasma metabolomic analyses (8 pathways; 354 metabolites) in 150 asymptomatic childhood cancer survivors previously treated with anthracyclines. Median time from cancer diagnosis to study participation was 12.4 years (2.6-37.9 years); 64% were treated for a hematologic malignancy; median anthracycline dose was 350 mg/m(2) (25-642 mg/m(2)). Thirty-five (23%) participants had cardiac dysfunction-defined as left ventricular end-systolic wall stress >2SD by echocardiogram. Plasma levels of 15 compounds in three metabolic pathways (carbohydrate, amino acid, and lipid metabolism) were significantly different between individuals with cardiac dysfunction and those with normal systolic function. After adjusting for multiple comparisons, individuals with cardiac dysfunction had significantly lower plasma carnitine levels [relative ratio (RR), 0.89; P < 0.01] in relation to those with normal systolic function. These findings may facilitate the development of primary prevention (treatment of carnitine deficiency before/during anthracycline administration) and secondary prevention strategies (screening and treatment in long-term survivors) in patients at highest risk for CHF. Cancer Epidemiol Biomarkers Prev; 23(6); 1109-14. ©2014 AACR.

Developmental impact and lesion maturation of histotripsy-mediated non-invasive tissue ablation in a fetal sheep model.

Non-invasive histotripsy therapy has previously been used to achieve precise fetal tissue ablation in a sheep model. To further assess the clinical viability of the technique, this study investigated potential effects of histotripsy therapy during the remaining gestation and its local impact on fetal development. Five ewes (six lambs) at 95-107 d of gestation were treated and allowed to complete the full gestation period of 150 d. A 1-MHz focused transducer was used to treat the fetal kidney and liver with 5-µs pulses at 500-Hz repetition rates and 10- to 16-MPa peak negative pressures; ultrasound imaging provided real-time treatment guidance. The lambs were euthanized after delivery and treated organs were harvested. Samples were examined by magnetic resonance imaging and histopathologic analysis. These data were compared with results from four other ewes (four lambs) that underwent similar treatments but were sacrificed immediately after the procedure. The sheep tolerated the treatment well, and acute lesion samples displayed well-defined ablated regions characterized by the presence of fractionated tissue and hemorrhage. All fetuses that were allowed to continue gestation survived and were delivered at full term. The lambs were healthy on delivery, with no signs of external injury. A minor indentation was observed in each of the treated kidneys with minimal presence of fibrous tissue, while no discernible signs of lesions were detected in treated livers. In a sheep model, histotripsy-mediated fetal tissue ablation caused no acute or pregnancy-related complications, supporting the potential safety and effectiveness of histotripsy therapy as a tool in fetal intervention procedures.

Strategies to prevent anthracycline-related congestive heart failure in survivors of childhood cancer.

Cardiovascular complications are a leading cause of therapy-related morbidity and mortality in long-term survivors of childhood malignancy. In fact, childhood cancer survivors are at a 15-fold risk of developing CHF compared to age-matched controls. There is a strong dose-dependent association between anthracycline exposure and risk of CHF, and the incidence increases with longer followup. Outcome following diagnosis of CHF is generally poor, with overall survival less than 50% at 5 years. The growing number of childhood cancer survivors makes it imperative that strategies be developed to prevent symptomatic heart disease in this vulnerable population. We present here an overview of the current state of knowledge regarding primary, secondary, and tertiary prevention strategies for childhood cancer survivors at high risk for CHF, drawing on lessons learned from prevention studies in nononcology populations as well as from the more limited experience in cancer survivors.

Use of a pressure guidewire in fetal cardiac intervention for critical aortic stenosis.

Fetal cardiac intervention for critical aortic stenosis (AS) with evolving hypoplastic left heart syndrome is performed in an attempt to maintain a biventricular circulation postnatally. The procedure has been hindered by technical challenges and poor candidate selection. We report here the novel use of a pressure guidewire during aortic valvuloplasty in a fetus at 21 weeks' gestation with critical AS and evolving hypoplastic left heart syndrome. Use of a pressure guidewire during fetal cardiac intervention offers several potential advantages over existing protocols. This technique augments fetal ultrasound as it relates to operator awareness of catheter and wire position (with continuous monitoring of pressure waveforms), improves on intraprocedural fetal hemodynamic monitoring and responsiveness to resuscitation, and provides a rich new data set of invasive fetal hemodynamics. This data set offers tremendous potential with regards to improving candidate selection and postintervention prognostication. In addition, we provide the first, to our knowledge, characterization of intracardiac pressures in a human fetus with congenital heart disease. Given the realized and potential benefits associated with this technique, use of a pressure guidewire may become standard of care for all fetal cardiac interventions.

Experience with CartoSound for arrhythmia ablation in pediatric and congenital heart disease patients.

PURPOSE: Electro-anatomic mapping (EAM) has been used for more than a decade to assist in defining arrhythmia propagation for transcatheter ablation. Intra-cardiac echocardiography (ICE) has also gained acceptance as an adjunct to further define intracardiac anatomy. The integration of these two technologies (CartoSound, Biosense-Webster, Diamond Bar, CA, USA) is a recent development. In this report, we describe our early experience in the young, with and without congenital heart defects (CHD). METHODS: The clinical and electrophysiologic records of the first 17 patients to undergo procedures with the CartoSound (EAM-ICE) system were reviewed. In all 17, the 3-dimensional shape of the chamber(s) of interest was created using serial tracing of ICE images. The ICE catheter was placed in the esophagus in three and through the femoral vein in 14. Descriptive analysis was performed on demographic data as well as procedural characteristics including procedure time, fluoroscopy time, geometry acquisition time, EAM duration, ablation time, procedure success, and complications. RESULTS: Arrhythmias comprised intra-atrial re-entry tachycardia (13 patients, 76%), Wolff-Parkinson-White syndrome (1; 6%), ventricular ectopic tachycardia (2; 12%), and atrioventricular node re-entrant tachycardia (1; 6%). Thirteen had CHD, with a median two palliative operations; six had single-ventricle anatomy. Procedure duration was 266 ± 134 min (median ± SD), and fluoroscopy time was 29 ± 28.3 min. Geometry acquisition took 41 ± 35.4 min, or 16% of the total case duration. Ablation lesions were placed in 16 cases, (cooled tip in 12) of which 15 (94%) were successful. One patient experienced mild hypotension. ICE image quality in three patients with the probe placed in the esophagus was suboptimal. CONCLUSIONS: Advantages of CartoSound appear to be (1) anatomy modeling in the shape imposed by the arrhythmia, (2) more accurate geometry than EAM alone, and (3) demonstration of catheter position and lesions on echo during the study. Perceived disadvantages are (1) the large sheath required for ICE (11F), and (2) significant procedure time devoted to creation of anatomy. Optimal use may be to focus on key structures required for ablation, obtaining additional views as needed.