Vigorous Exercise in Patients With Hypertrophic Cardiomyopathy.

Importance: Whether vigorous intensity exercise is associated with an increase in risk of ventricular arrhythmias in individuals with hypertrophic cardiomyopathy (HCM) is unknown. Objective: To determine whether engagement in vigorous exercise is associated with increased risk for ventricular arrhythmias and/or mortality in individuals with HCM. The a priori hypothesis was that participants engaging in vigorous activity were not more likely to have an arrhythmic event or die than those who reported nonvigorous activity. Design, Setting, and Participants: This was an investigator-initiated, prospective cohort study. Participants were enrolled from May 18, 2015, to April 25, 2019, with completion in February 28, 2022. Participants were categorized according to self-reported levels of physical activity: sedentary, moderate, or vigorous-intensity exercise. This was a multicenter, observational registry with recruitment at 42 high-volume HCM centers in the US and internationally; patients could also self-enroll through the central site. Individuals aged 8 to 60 years diagnosed with HCM or genotype positive without left ventricular hypertrophy (phenotype negative) without conditions precluding exercise were enrolled. Exposures: Amount and intensity of physical activity. Main Outcomes and Measures: The primary prespecified composite end point included death, resuscitated sudden cardiac arrest, arrhythmic syncope, and appropriate shock from an implantable cardioverter defibrillator. All outcome events were adjudicated by an events committee blinded to the patient's exercise category. Results: Among the 1660 total participants (mean [SD] age, 39 [15] years; 996 male [60%]), 252 (15%) were classified as sedentary, and 709 (43%) participated in moderate exercise. Among the 699 individuals (42%) who participated in vigorous-intensity exercise, 259 (37%) participated competitively. A total of 77 individuals (4.6%) reached the composite end point. These individuals included 44 (4.6%) of those classified as nonvigorous and 33 (4.7%) of those classified as vigorous, with corresponding rates of 15.3 and 15.9 per 1000 person-years, respectively. In multivariate Cox regression analysis of the primary composite end point, individuals engaging in vigorous exercise did not experience a higher rate of events compared with the nonvigorous group with an adjusted hazard ratio of 1.01. The upper 95% 1-sided confidence level was 1.48, which was below the prespecified boundary of 1.5 for noninferiority. Conclusions and Relevance: Results of this cohort study suggest that among individuals with HCM or those who are genotype positive/phenotype negative and are treated in experienced centers, those exercising vigorously did not experience a higher rate of death or life-threatening arrhythmias than those exercising moderately or those who were sedentary. These data may inform discussion between the patient and their expert clinician around exercise participation.

Inter-observer and Inter-vendor Variability in Strain Measurements in Patients with Single Right Ventricular Anatomy.

Myocardial strain offers new insights into ventricular performance, There are software packages from several different companies used to ascertain this, and little data is available in patients with single right ventricle (sRV) physiology. We aimed to compare the analysis of two strain software applications using a cohort of patients with sRV for both inter-vendor and inter-observer variability. Echocardiograms from 85 patients with sRV (122 separate studies) were prospectively evaluated. All had Glenn and/or Fontan palliation. Longitudinal 4-chamber (4LS), inflow/outflow (IO), circumferential, and radial strain were assessed using Velocity Vector Imaging (VVI, Seimens, Munich) and Automated Functional Imaging (AFI, General Electric, Boston) software. In a subset of 45 patients (61 separate studies), strain measurements were obtained by two sonographers so a paired "inter-observer" analysis could be performed. A moderate correlation between measurements made by the two systems was observed. Circumferential strain assessment had the highest R value (0.77) with all others having R values < 0.6. Both software packages showed modest inter-observer reproducibility for longitudinal and circumferential strain. VVI intraclass correlation coefficients (ICC) for 4LS and average circumferential strain (ACS) were 0.6 and 0.58, compared to 0.68 and 0.59 for AFI. Other than radial strain and VVI IO inferior strain, mean strain differences between AFI and VVI were ≤ 1%. Inter-observer variability is modest, however, mean differences are minimal suggesting reasonable clinical reliability. Inter-vendor variability is greater and not as clinically reliable. In patients with sRV, serial assessments with strain should be performed using the same software.

The Use of Virtual Reality Echocardiography in Medical Education.

Virtual reality (VR) is a relatively new technology that allows an individual to experience a virtual world. This new immersive video type may be of particular usefulness in procedure-based healthcare settings. We hypothesized that VR echocardiography was non-inferior to live demonstration. Our aim was to assess the usefulness of a VR echocardiographic approach in teaching echocardiography to pediatric trainees compared to live demonstration. This was a single center, cross-sectional observational design. We used a Garmin VIRB® 360 and a head-mount display to record live echocardiography exams in a pediatric population. An Oculus Go™ was used to view the 360° immersive/VR videos. Trainees responded to a written questionnaire afterwards. Fifteen trainees participated in the study, each of whom had previously seen echocardiography through live demonstration teaching. Eleven respondents had previous hands-on echocardiography experience. All 15 participants confirmed that VR echocardiography is a useful teaching tool with 87% (n = 13) rating it as good or very good on a 5-point Likert scale. When asked to compare VR to live demonstration, 67% (n = 10) rated VR echocardiography as the same or better than live demonstration. One of the participants reported a side effect, namely mild and self-resolving dizziness. VR echocardiography is a safe, inexpensive and practical way for trainees to learn echocardiography. The addition of VR echocardiography to the arsenal of teaching tools may enrich the learning experience for trainees.

Echocardiography-Guided Risk Stratification for Long QT Syndrome.

BACKGROUND: The ability to identify those patients at the highest phenotypic risk for long QT syndrome (LQTS)-associated life-threatening cardiac events remains suboptimal. OBJECTIVES: This study sought to validate the association between electromechanical window (EMW) negativity, as derived from echocardiography, and symptomatic versus asymptomatic status in patients with LQTS. METHODS: We analyzed a cohort of 651 patients with LQTS (age 26 ± 17 years; 60% females; 158 symptomatic; 51% LQTS type 1; 33% LQTS type 2; 11% LQTS type 3; 5% multiple mutations) and 50 healthy controls. EMW was calculated as the difference between the interval from QRS onset to aortic valve closure midline, as derived for continuous-wave Doppler, and the electrocardiogram-derived QT interval for the same beat. RESULTS: A negative EMW was found among nearly all patients with LQTS compared to controls, with more profound EMW negativity in patients with symptomatic LQTS compared to those with asymptomatic LQTS (-52 ± 38 ms vs. -18 ± 29 ms; p < 0.0001). Logistic regression identified EMW, heart rate-corrected QT interval (QTc), female sex, and LQTS genotype as univariate predictors of symptomatic status. After multivariate analysis, EMW remained an independent predictor of symptomatic status (odds ratio for each 10-ms decrease in EMW: 1.37; 95% confidence interval: 1.27 to 1.48; p < 0.0001). EMW outperformed QTc in predicting symptomatic patients (area under the curve: 0.78 vs. 0.70; p = 0.01). After training and implementation, EMW correlation from echocardiographic sonographers showed excellent reliability (intraclass correlation coefficient: 0.93; 95% confidence interval: 0.89 to 0.96). CONCLUSIONS: In this validation study, patients with a history of LQTS-associated life-threatening cardiac events had a more profoundly negative EMW. EMW outperformed heart rate-corrected QT interval as a predictor of symptomatic status. EMW is now a clinically validated risk factor. In December 2019, our institution's echocardiography clinical practice committee approved use of EMW for patients with LQTS, making it a routinely reported echocardiographic finding.

Left ventricular diastolic dysfunction in HIV-uninfected infants exposed in utero to antiretroviral therapy.

OBJECTIVES: To longitudinally measure LV diastolic function in HIV-exposed but uninfected (HEU) children perinatally exposed to ART. DESIGN: HEU children who were perinatally exposed to antiretroviral therapy (ART) may be at risk for adverse cardiac effects. We have previously reported that those children have decreased left ventricular (LV) mass, dimension, and septal thickness with increased contractility. METHODS: Serial echocardiograms were obtained at specific times from birth to 48 months from two groups of HIV-uninfected children: 148 HIV-negative children who were perinatally exposed to ART and 130 non-ART-exposed HIV-unexposed healthy controls. The following LV diastolic indices were obtained: mitral valve early and late diastolic velocity (E and A), tissue Doppler-derived LV-free wall and septal early diastolic velocity (LV e' and sep e'). RESULTS: All echocardiographic indices were significantly different in ART-exposed children compared with ART-unexposed healthy controls. Both E and A were overall lower at all ages by 8.28 cm/s (P = 0.0002) and 13.46 cm/s (P < 0.0001) respectively. E/A ratio was higher by 0.27, 0.46, and 0.28 units at birth, 1 year and 2 years of age, respectively (all P ≤ 0.01). Moreover, LV e' and sep e' were overall lower at all ages by 0.84 cm/s (P = 0.01) and 0.47 cm/s (P = 0.02), respectively. CONCLUSION: Children who were exposed to ART in utero have subclinical yet significant differences in specific LV diastolic indices. Follow-up with serial echocardiograms are recommended in this population to further assess the potential cardiac toxicity of perinatal exposure to ART.

Lambl's excrescences in children: Improved detection via transthoracic echocardiography.

BACKGROUND: Lambl's excrescences (LE) are fibrous extensions that can be found along the lines of closure of the aortic valve. Due to improvements in ultrasound technology, LE are frequently imaged during transthoracic echocardiography (TTE) in adults. OBJECTIVE: The purpose of this study was to determine the prevalence of LE among children from two eras (2004-2006 and 2011-2012) and the effect of technological advancements on LE detection. METHODS: TTE from 700 subjects (age 18 years old or younger) were reviewed. All parasternal long and short axis images of the aortic valve were reviewed by a board certified echocardiographer, and the positive studies were then reviewed by two additional observers to confirm the presence of LE. A two-sample t test with 95% significance was used to analyze the presence of LE in the cohorts. Median follow-up duration was 66 months. RESULTS: Of the 700 subjects, 12 (1.7%) children were found to have LE. No significant difference in prevalence was found between the two eras (.9% vs. 2.6%, P = .08) and the presence of LE was not related to age (P = .36). The youngest subject with an LE was 5 months old. During long-term follow-up there were no clinical events in the 12 children identified with a LE. CONCLUSIONS: The prevalence of LE in children is lower than that reported in adults, this supports the age-related "wear and tear" process that has been described in previous studies. LE do not require intervention or more aggressive invasive imaging in children.

Application of the Pediatric Appropriate Use Criteria for Chest Pain.

OBJECTIVES: To characterize the subgroup of outpatient pediatric patients presenting with chest pain and to determine the effectiveness of published pediatric appropriate use criteria (PAUC) to detect pathology. STUDY DESIGN: The Pediatric Appropriate Use of Echocardiography study evaluated the use and yield of transthoracic echocardiography (TTE) before and after PAUC release. Data were reviewed on patients ?18 years of age who underwent TTE for chest pain. Indications were classified as appropriate (A), may be appropriate (M), and rarely appropriate (R) based on PAUC ratings, and findings were normal, incidental, or abnormal. RESULTS: Chest pain was the primary indication in 772 of 4562 outpatient TTE studies (17%) (median age 14 years, IQR 10-16) ordered during the study period: 458 of 772 before (59%) and 314 of 772 after (41 %) the release of PAUC with no change in appropriateness. In A indications (n?=?654), 642 (98%) were normal, 5 (1%) had incidental findings, and 7 (1%) were abnormal. A and M detected 100% of all abnormal findings (A: n?=?7; M: n?=?6; R: n?=?0), with an association between ratings and findings (P?<.001). There was no association between R rating and any pathology. CONCLUSIONS: There was no change in ordering patterns with publication of the PAUC. Despite the high rate of TTEs ordered for indications rated A, most studies were normal. Studies that detected pathology were performed for indications rated A or M, but not R. This study supports PAUC as a useful tool in pediatric chest pain evaluation that may subsequently improve the use of TTE.

Educational intervention for improving the appropriateness of transthoracic echocardiograms ordered by pediatric cardiologists.

OBJECTIVE: The objective of this study was to evaluate effectiveness of educational intervention (EI) in the Pediatric Appropriate Use of Echocardiography (PAUSE) study to improve appropriateness of transthoracic echocardiograms (TTEs) ordered in pediatric cardiology clinics. DESIGN: Data were prospectively collected after the publication of the Appropriate Use Criteria (AUC) document during 2 phases: the pre-EI phase (1/1/15 to 4/30/15) and the post-EI phase (7/1/15 to 10/30/15). Pre-EI, site-investigators (SI) determined AUC indications, by reviewing the clinic records. Post-EI, providers assigned indications prior to obtaining TTE. SETTING: Pediatric cardiology clinics at six centers. PATIENTS: Those ≤18 years old, receiving initial outpatient TTE. INTERVENTIONS: EI included (i) sharing the pre-EI appropriateness ratings with providers, (ii) lecture on AUC, (iii) providers self-assigning indications, and (iv) monthly e-mail feedback by SI to individual providers. OUTCOME: The primary outcome measure was a change in the proportion of studies for indications rated R following EI. RESULTS: Of the 4542 TTEs (1907 pre-EI, 2635 post-EI) ordered by 90 physicians, overall comparison of appropriateness ratings before and after EI showed an increase in Appropriate (72.5%-76.2%, P = .004), no change in May Be Appropriate, and a decline in Rarely Appropriate (R) from 9.6% to 7.4%, P = .008. Following EI, a significant decline in R was observed only in three centers and EI did not affect the variation in TTEs ordered for R indications among physicians (P = .467). Physicians with the highest proportion of TTEs ordered for R before EI, showed the most significant decline in R. CONCLUSIONS: Appropriateness of pediatric outpatient TTE varies substantially by center. A customized EI resulted in modest improvement in the appropriateness of TTEs in the PAUSE study, with an increase in Appropriate and a decrease in R TTEs. Multifaceted EIs are required to improve adherence to national standards such as AUC.

Application of pediatric appropriate use criteria for initial outpatient evaluation of syncope.

BACKGROUND: Syncope is a common reason for outpatient transthoracic echocardiography (TTE). We studied the applicability of pediatric appropriate use criteria (AUC) on initial outpatient evaluation of children (≤18 years) with syncope. METHODS: Data were obtained before (Phase I, April-September 2014) and after (Phase II, January-April 2015) the release of the AUC document from six participating pediatric cardiology centers. Site investigators determined the indication for TTE and assigned appropriateness rating based on the AUC document: Appropriate (A), May Be Appropriate (M), Rarely Appropriate (R), or "unclassifiable" (U) if it did not fit any scenario in the AUC document. RESULTS: Of the total 4562 TTEs, 310 (6.8%) were performed for syncope: 174/2655 (6.6%) Phase I and 136/1907 (7.1%) Phase II, P=.44. Overall, 168 (50.5%) were for indications rated A, 63 (18.9%) for M, 79 (23.7%) for R, and 23 (6.9%) for U. Release of AUC did not change the appropriateness of TTEs [A=51.6% vs 49.0%, P=.63, R=20.2% vs 28.3%, P=.09]. Overall syncope-related R indications formed 15.7% of R indications for all the echocardiograms performed in the entire Pediatric Appropriate Use (PAUSE) study (11.9% Phase I and 22.4% Phase II, P=.002). TTEs were normal in majority of the patients except 7 that had incidental findings. CONCLUSIONS: In conclusion, syncope is a common reason for indications rated R and release of the AUC document did not improve appropriate utilization of TTE in syncope. Targeted educational interventions are needed to reduce unnecessary TTEs in children with syncope.