Early outcomes of moderate-to-high-risk pediatric congenital cardiac surgery and predictors of extracorporeal circulatory life support requirement.

Background: Cardiopulmonary failure refractory to medical management after moderate-to-high-risk congenital cardiac surgery may necessitate mechanical support with veno-arterial extracorporeal membrane oxygenation (ECMO). On the extreme, ECMO can also be initiated in the setting of cardiac arrest (extracorporeal cardiopulmonary resuscitation, ECPR) unresponsive to conventional resuscitative measures. Methods: This was a single-center retrospective cohort study of patients (n = 510) aged <3 years old who underwent cardiac surgery with cardiopulmonary bypass with a RACHS-1 score ≥3 between 2011 and 2014. Perioperative factors were reviewed to identify predictors of ECMO initiation and mortality in the operating room (OR) and the intensive care unit (ICU). Results: A total of 510 patients with a mean surgical age of 10.0 ± 13.4 months were included. Among them, 21 (4%) patients received postoperative ECMO-12 were initiated in the OR and 9 in the ICU. ECMO cannulation was associated with cardiopulmonary bypass duration, aortopulmonary shunt, residual severe mitral regurgitation, vaso-inotropic score, and postprocedural lactate (p < 0.001). Of the 32 (6%) total deaths, 7 (22%) were ECMO patients-4 were elective OR cannulations and 3 were ICU ECPR. Prematurity [hazard ratio (HR): 2.61, p < 0.01), Norwood or Damus-Kaye-Stansel procedure (HR: 4.29, p < 0.001), postoperative left ventricular dysfunction (HR: 5.10, p = 0.01), residual severe tricuspid regurgitation (HR: 6.06, p < 0.001), and postoperative ECMO (ECPR: HR: 15.42, p < 0.001 vs. elective: HR: 5.26, p = 0.01) were associated with mortality. The two patients who were electively cannulated in the ICU survived. Discussion: Although uncommon, postoperative ECMO in children after congenital cardiac surgery is associated with high mortality, especially in cases of ECPR. Patients with long cardiopulmonary bypass time, residual cardiac lesions, or increased vaso-inotropic requirement are at higher risk of receiving ECMO. Pre-emptive or early ECMO initiation before deterioration into cardiac arrest may improve survival.

Reimplantation of the aortic valve in patients with tricuspid aortic valve: the Toronto General Hospital experience.

Background: Aortic valve sparing operations were introduced three decades ago but controversy remains regarding its appropriateness, reproducibility and durability. This article describes the long-term outcomes of patients who had reimplantation of the aortic valve. Methods: All patients who had reimplantation of a tricuspid aortic valve at Toronto General Hospital from 1989 through 2019 were selected for this study. Patients were followed prospectively with periodical clinical assessments and imaging of the heart and aorta. Results: Four hundred and four patients were identified. The median age was 48.0 [interquartile range (IQR), 35.0-59.0] years and 310 (76.7%) were men. There were 150 patients with Marfan syndrome, 20 with Loeys-Dietz syndrome and 33 with acute or chronic aortic dissections. The median follow-up was 11.7 (IQR, 6.8-17.1) years. There were 55 patients alive and without reoperation at 20 years. The cumulative mortality at 20 years was 26.7% [95% confidence interval (CI): 20.6-34.2%], the cumulative incidence of reoperation on the aortic valve was 7.0% (95% CI: 4.0-12.2%) and the development of moderate or severe aortic insufficiency was 11.8% (95% CI: 8.5-16.5%). We could not identify variables associated with reoperation on the aortic valve or with the development of aortic insufficiency. New distal aortic dissections were common in patients with associated genetic syndromes. Conclusions: Reimplantation of the aortic valve in patients with tricuspid aortic valve provides excellent aortic valve function during the first two decades of follow-up. Distal aortic dissections are relatively common in patients with associated genetic syndromes.

Comprehensive Cardiovascular Magnetic Resonance Tissue Characterization and Cardiotoxicity in Women With Breast Cancer.

Importance: There is a growing interest in understanding whether cardiovascular magnetic resonance (CMR) myocardial tissue characterization helps identify risk of cancer therapy-related cardiac dysfunction (CTRCD). Objective: To describe changes in CMR tissue biomarkers during breast cancer therapy and their association with CTRCD. Design, Setting, and Participants: This was a prospective, multicenter, cohort study of women with ERBB2 (formerly HER2)-positive breast cancer (stages I-III) who were scheduled to receive anthracycline and trastuzumab therapy with/without adjuvant radiotherapy and surgery. From November 7, 2013, to January 16, 2019, participants were recruited from 3 University of Toronto-affiliated hospitals. Data were analyzed from July 2021 to June 2022. Exposures: Sequential therapy with anthracyclines, trastuzumab, and radiation. Main Outcomes and Measures: CMR, high-sensitivity cardiac troponin I (hs-cTnI), and B-type natriuretic peptide (BNP) measurements were performed before anthracycline treatment, after anthracycline and before trastuzumab treatment, and at 3-month intervals during trastuzumab therapy. CMR included left ventricular (LV) volumes, LV ejection fraction (EF), myocardial strain, early gadolinium enhancement imaging to assess hyperemia (inflammation marker), native/postcontrast T1 mapping (with extracellular volume fraction [ECV]) to assess edema and/or fibrosis, T2 mapping to assess edema, and late gadolinium enhancement (LGE) to assess replacement fibrosis. CTRCD was defined using the Cardiac Review and Evaluation Committee criteria. Fixed-effects models or generalized estimating equations were used in analyses. Results: Of 136 women (mean [SD] age, 51.1 [9.2] years) recruited from 2013 to 2019, 37 (27%) developed CTRCD. Compared with baseline, tissue biomarkers of myocardial hyperemia and edema peaked after anthracycline therapy or 3 months after trastuzumab initiation as demonstrated by an increase in mean (SD) relative myocardial enhancement (baseline, 46.3% [16.8%] to peak, 56.2% [18.6%]), native T1 (1012 [26] milliseconds to 1035 [28] milliseconds), T2 (51.4 [2.2] milliseconds to 52.6 [2.2] milliseconds), and ECV (25.2% [2.4%] to 26.8% [2.7%]), with P <.001 for the entire follow-up. The observed values were mostly within the normal range, and the changes were small and recovered during follow-up. No new replacement fibrosis developed. Increase in T1, T2, and/or ECV was associated with increased ventricular volumes and BNP but not hs-cTnI level. None of the CMR tissue biomarkers were associated with changes in LVEF or myocardial strain. Change in ECV was associated with concurrent and subsequent CTRCD, but there was significant overlap between patients with and without CTRCD. Conclusions and Relevance: In women with ERBB2-positive breast cancer receiving sequential anthracycline and trastuzumab therapy, CMR tissue biomarkers suggest inflammation and edema peaking early during therapy and were associated with ventricular remodeling and BNP elevation. However, the increases in CMR biomarkers were transient, were not associated with LVEF or myocardial strain, and were not useful in identifying traditional CTRCD risk.

Closure of Left Atrial Appendage Has no Effect on Thromboembolic Rates after Mitral Valve Repair in Patients in Sinus Rhythm.

Closure of the left atrial appendage (LAA) reduces the rates of TIA/stroke in patients in atrial fibrillation (AF) but its role in patients in sinus rhythm who undergo mitral valve repair (MV) for leaflet prolapse remains unknown. This study examined the effects of closing the LAA in TIA/stroke after MV repair. Our database on patients who had MV repair for leaflet prolapse from 2000 through 2019 was reviewed. After excluding patients at higher risk of TIA/stroke, 1050 patients in sinus rhythm were entered into the study: 781 with open LAA and 269 with surgically closed LAA. Using a propensity score analysis to compensate from clinical differences, 267 pairs of patients with open and closed LAA were matched. Follow-up was truncated at 5 years because routine closure of the LAA was performed only during recent years. The cumulative incidence of TIA/stroke at 5 years in the entire cohort was 2.7% [95% CI 1.9, 4.0]; it was 2.9% [95% CI 1.9, 4.4] in patients with open LAA,and 1.8% [95% CI 0.7, 4.9] in patients with closed LAA (P = 0.53). In the matched cohorts, the cumulative incidences of TIA/stroke did not differ significantly (match-adjusted HR [95% CI] = 0.80 [0.21, 2.98], P = 0.74), and multivariable Cox proportional hazard regression analysis also confirmed no difference in the risk of TIA/stroke between the 2 groups (regression-adjusted HR [95% CI] = 0.58 [0.12, 2.9], P = 0.47). This study failed to show a reduction in the risk of TIA/stroke by closing the LAA in patients in sinus rhythm (Figure 6). Closure of the LAA during MV repair warrants a larger and more rigorous study.

Self-Reported Physical Activity, QoL, Cardiac Function, and Cardiorespiratory Fitness in Women With HER2+ Breast Cancer.

Background: Women treated for breast cancer are at risk for worsening health-related quality of life (QoL), cardiac function, and cardiorespiratory fitness. Objectives: The aim of this study was to assess the associations of self-reported moderate to vigorous intensity physical activity (MVPA) during cancer treatment with concurrent measures of QoL and cardiac function and with post-treatment cardiorespiratory fitness in women with human epidermal growth factor receptor 2-positive breast cancer receiving sequential anthracyclines and trastuzumab. Methods: EMBRACE-MRI 1 (Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI) study participants who completed questionnaires for MVPA (modified Godin Leisure Time Physical Activity Questionnaire) and QoL (EQ-5D-3L, Minnesota Living With Heart Failure Questionnaire) and cardiac imaging every 3 months during treatment and post-treatment cardiopulmonary exercise testing were included. Participants engaging in ≥90 minutes of MVPA each week were labeled "active." Generalized estimation equations and linear regression analyses were used to assess concurrent and post-treatment associations with MVPA and activity status, respectively. Results: Eighty-eight participants were included (mean age 51.4 ± 8.9 years). Mean MVPA minutes, QoL, and cardiac function (left ventricular ejection fraction, global longitudinal strain, E/A ratio, and E/e' ratio) worsened by 6 months into trastuzumab therapy. Higher MVPA (per 30 minutes) during treatment was associated with better concurrent overall (ß = -0.42) and physical (ß = -0.24) Minnesota Living With Heart Failure Questionnaire scores, EQ-5D-3L index (ß = 0.003), visual analogue scale score (ß = 0.43), diastolic function (E/A ratio; ß = 0.01), and global longitudinal strain (ß = 0.04) at each time point (P ≤ 0.01 for all). Greater cumulative MVPA over the treatment period was associated with higher post-treatment cardiorespiratory fitness (peak oxygen consumption; ß = 0.06 per 30 minutes; P < 0.001). Conclusions: Higher self-reported MVPA during treatment for human epidermal growth factor receptor 2-positive breast cancer was associated with better QoL and diastolic and systolic left ventricular function measures during treatment and better post-treatment cardiorespiratory fitness.

A Combined Echocardiography Approach for the Diagnosis of Cancer Therapy-Related Cardiac Dysfunction in Women With Early-Stage Breast Cancer.

IMPORTANCE: Diagnosis of cancer therapy-related cardiac dysfunction (CTRCD) remains a challenge. Cardiovascular magnetic resonance (CMR) provides accurate measurement of left ventricular ejection fraction (LVEF), but access to repeated scans is limited. OBJECTIVE: To develop a diagnostic model for CTRCD using echocardiographic LVEF and strain and biomarkers, with CMR as the reference standard. DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study, patients were recruited from University of Toronto-affiliated hospitals from November 2013 to January 2019 with all cardiac imaging performed at a single tertiary care center. Women with human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer were included. The main exclusion criterion was contraindication to CMR. A total of 160 patients were recruited, 136 of whom completed the study. EXPOSURES: Sequential therapy with anthracyclines and trastuzumab. MAIN OUTCOMES AND MEASURES: Patients underwent echocardiography, high-sensitivity troponin I (hsTnI), B-type natriuretic peptide (BNP), and CMR studies preanthracycline and postanthracycline every 3 months during and after trastuzumab therapy. Echocardiographic measures included 2-dimensional (2-D) LVEF, 3-D LVEF, peak systolic global longitudinal strain (GLS), and global circumferential strain (GCS). LVEF CTRCD was defined using the Cardiac Review and Evaluation Committee Criteria, GLS or GCS CTRCD as a greater than 15% relative change, and abnormal hsTnI and BNP as greater than 26 pg/mL and ≥ 35 pg/mL, respectively, at any follow-up point. Combinations of echocardiographic measures and biomarkers were examined to diagnose CMR CTRCD using conditional inference tree models. RESULTS: Among 136 women (mean [SD] age, 51.1 [9.2] years), CMR-identified CTRCD occurred in 37 (27%), and among those with analyzable images, in 30 of 131 (23%) by 2-D LVEF, 27 of 124 (22%) by 3-D LVEF, 53 of 126 (42%) by GLS, 61 of 123 (50%) by GCS, 32 of 136 (24%) by BNP, and 14 of 136 (10%) by hsTnI. In isolation, 3-D LVEF had greater sensitivity and specificity than 2-D LVEF for CMR CTRCD while GLS had greater sensitivity than 2-D or 3-D LVEF. Regression tree analysis identified a sequential algorithm using 3-D LVEF, GLS, and GCS for the optimal diagnosis of CTRCD (area under the receiver operating characteristic curve, 89.3%). The probability of CTRCD when results for all 3 tests were negative was 1.0%. When 3-D LVEF was replaced by 2-D LVEF in the model, the algorithm still performed well; however, its primary value was to rule out CTRCD. Biomarkers did not improve the ability to diagnose CTRCD. CONCLUSIONS AND RELEVANCE: Using CMR CTRCD as the reference standard, these data suggest that a sequential approach combining echocardiographic 3-D LVEF with 2-D GLS and 2-D GCS may provide a timely diagnosis of CTRCD during routine CTRCD surveillance with greater accuracy than using these measures individually. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02306538.

Sparing the Prod: Providing an Alternative to Endomyocardial Biopsies With Noninvasive Surveillance After Heart Transplantation During COVID-19.

Background: The COVID-19 pandemic has reduced access to endomyocardial biopsy (EMB) rejection surveillance in heart transplant (HT) recipients. This study is the first in Canada to assess the role for noninvasive rejection surveillance in personalizing titration of immunosuppression and patient satisfaction post-HT. Methods: In this mixed-methods prospective cohort study, adult HT recipients more than 6 months from HT had their routine EMBs replaced by noninvasive rejection surveillance with gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) testing. Demographics, outcomes of noninvasive surveillance score, hospital admissions, patient satisfaction, and health status on the medical outcomes study 12-item short-form health survey (SF-12) were collected and analyzed, using t tests and χ2 tests. Thematic qualitative analysis was performed for open-ended responses. Results: Among 90 patients, 31 (33%) were enrolled. A total of 36 combined GEP/dd-cfDNA tests were performed; 22 (61%) had negative results for both, 10 (27%) had positive GEP/negative dd-cfDNA results, 4 (11%) had negative GEP/positive dd-cfDNA results, and 0 were positive on both. All patients with a positive dd-cfDNA result (range: 0.19%-0.81%) underwent EMB with no significant cellular or antibody-mediated rejection. A total of 15 cases (42%) had immunosuppression reduction, and this increased to 55% in patients with negative concordant testing. Overall, patients' reported satisfaction was 90%, and on thematic analysis they were more satisfied, with less anxiety, during the noninvasive testing experience. Conclusions: Noninvasive rejection surveillance was associated with the ability to lower immunosuppression, increase satisfaction, and reduce anxiety in HT recipients, minimizing exposure for patients and providers during a global pandemic.

Contexte: La pandémie de COVID-19 a réduit l'accès à la biopsie endomyocardique pour surveiller le risque de rejet après une greffe du cœur. Cette étude est la première à être menée au Canada pour évaluer le rôle de la surveillance non invasive du risque de rejet en personnalisant le titrage de l'immunosuppression et la satisfaction du patient après la greffe cardiaque. Méthodologie: Dans le cadre de cette étude de cohorte prospective à méthodes mixtes, des adultes ayant reçu une greffe cardiaque depuis plus de six mois ont vu leurs biopsies endomyocardiques régulières remplacées par une surveillance non invasive du risque de rejet qui consiste à établir le profil de l'expression génique et à analyser l'ADN acellulaire dérivé du donneur. Les données démographiques, les résultats du score de surveillance non invasive, les admissions à l'hôpital, la satisfaction des patients et l'état de santé tirés du questionnaire SF-12 (questionnaire abrégé sur la santé comprenant 12 items) de l'étude sur les issues médicales ont été colligés et analysés au moyen des tests T et des tests χ2. Les réponses ouvertes ont fait l'objet d'une analyse qualitative thématique. Résultats: Parmi 90 patients, 31 (33 %) ont été recrutés. Au total, 36 tests combinés de profilages de l'expression génique et d'ADN acellulaire dérivé du donneur ont été réalisés; les résultats ont été négatifs pour les deux tests dans 22 cas (61 %), positifs pour le profilage de l'expression génique et négatifs pour l'ADN acellulaire dans 10 cas (27 %), négatifs pour le profilage de l'expression génique et positifs pour l'ADN acellulaire dans quatre cas (11 %) et aucun cas n'a donné de résultats positifs pour les deux types de tests. Tous les patients qui ont donné des résultats positifs à l'analyse de l'ADN acellulaire dérivé du donneur (fourchette : 0,19 % à 0,81 %) ont subi une biopsie endomyocardique n'ayant révélé aucun rejet cellulaire ou à médiation par anticorps important. Au total, 15 cas (42 %) affichaient une immunosuppression réduite, proportion qui a grimpé à 55 % chez les patients dont les tests de concordance ont donné des résultats négatifs. Dans l'ensemble, le niveau de satisfaction rapporté par les patients était de 90 % et, à l'analyse thématique, ils étaient plus satisfaits et moins anxieux pendant les tests non invasifs. Conclusions: La surveillance non invasive du risque de rejet a été associée à la capacité de diminuer l'immunosuppression, d'augmenter la satisfaction et de réduire l'anxiété chez les patients qui ont reçu une greffe cardiaque, en plus de réduire l'exposition des patients et du personnel médical dans le contexte d'une pandémie.

Evaluation of Risk Prediction Models to Identify Cancer Therapeutics Related Cardiac Dysfunction in Women with HER2+ Breast Cancer.

Cancer-therapeutics-related cardiac dysfunction (CTRCD) is an important concern in women receiving trastuzumab therapy for HER2+ breast cancer. However, the ability to assess CTRCD risk remains limited. In this retrospective cohort study, we apply three published risk prediction models (Ezaz et al., NSABP-31 cardiac risk scores (CRS), and HFA-ICOS trastuzumab proforma) to 629 women (mean age 52.4 ± 10.9 years) with Stage I-III HER2+ breast cancer treated with trastuzumab ± anthracyclines to assess their performance to identify CTRCD during or immediately post treatment. Using these models, patients were classified into CTRCD risk categories according to the pre-treatment characteristics. With NSABP-31 CRS and HFA-ICOS proformas, patients in the highest risk category had a 1.7-to-2.4-fold higher relative risk of CTRCD than the low-risk category (p = 0.010 and 0.005, respectively). However, with all three risk models, those in the low-risk category had a high absolute risk of CTRCD (15.5-25.5%). The discrimination of the models for CTRCD (AUC 0.51-0.60) and their calibration was limited. NSAP-31 CRS and HFA-ICOS proformas can identify relative differences in CTRCD risk between patients, but when considering absolute risk, they are only able to identify the highest risk patients. There remains an ongoing need for accurate CTRCD risk prediction models in women with HER2+ breast cancer.

Risk factors for postoperative hyperglycemia in neonates.

OBJECTIVE: Postoperative hyperglycemia has been shown to be associated with higher morbidity and mortality in pediatric patients. Data on risk factors for neonatal patients is limited. The objective of this study was to identify pre- and intraoperative risk factors associated with postoperative glucose in neonates. METHODS: We conducted a retrospective cohort study of neonates after surgical procedures between January and December 2016 in a quaternary neonatal intensive care unit. The primary outcome was hyperglycemia defined as serum glucose ≥8.3 mmol/L during the first 4 hours postoperatively. Secondary outcomes included death and length of stay. We assessed the association of risk factors with the postoperative glucose. RESULTS: In total, 206 surgical procedures (171 patients) were evaluated, among which 178 had serum glucose values during the first 4 hours postoperatively available. The incidence of hyperglycemia was 54% (n = 96). The median (IQR) glucose during the first 4 hours in NICU was 8.4 (6.52-10.65) mmol/L. Risk factors for postoperative hyperglycemia were intraoperative glucose infusion rate (GIR) and gestational age. There was a non-linear relationship between gestational age and postoperative hyperglycemia. Mortality occurred in 6 (7%) in the no-hyperglycemia group and 3 (3%) in the hyperglycemia group (p = 0.31). CONCLUSIONS: Among the risk factors, intraoperative GIR was identified as a modifiable factor that can reduce postoperative hyperglycemia. A non-linear relationship of gestational age with postoperative glucose provides new insights that may help advance our understanding of the complex mechanisms of glucose homeostasis in neonates.

Can We Still Improve Survival Outcomes of Neonatal Biventricular Repairs?

BACKGROUND: We sought to identify modifiable factors to improve survival of neonatal biventricular repair by analyzing the cause of death and predictors of mortality and reintervention in the last 2 decades. METHODS: Between 1995 and 2016, 991 consecutive neonates were included. The cohort was divided by era: era I was from 1995 to 1999, era II 2000 to 2007, and era III 2008 to 2016. The Kaplan-Meier method was used to estimate freedom from death and reintervention. Univariable and multivariable Cox regression was applied to assess predictors for mortality or reintervention in the contemporary cohorts (2000-2016). RESULTS: Median age was 8 days (range, 5-13), and median body weight at operation was 3.3 kg (range, 2.9-3.6). The most common diagnosis was transposition with intact ventricular septum (32%), followed by transposition with ventricular septal defect (14.5%), and simple left-to-right shunt lesion (10.9%). There was significant improvement in survival from era I to eras II and III but no difference between eras II and III (1 year: 82.1% vs 89.4% vs 89.6%, respectively; P < .001). The most common cause of death was sudden death in eras I and III and cardiac in era II. Multivariable analysis revealed preoperative (P = .005)/postoperative (P < .001) extracorporeal membrane oxygenation and postoperative renal replacement (P < .001) as independent predictors for mortality. The reintervention rates were comparable between eras II and III (P = .53). Atrioventricular septal defects and common atrial trunk were identified as predictors for reintervention. CONCLUSIONS: Survival after neonatal biventricular repair remained unchanged. Preventing sudden death, myocardial protection, and minimizing residual lesions are potential targets to improve outcomes.

Association between genetic variants in the HIF1A-VEGF pathway and left ventricular regional myocardial deformation in patients with hypertrophic cardiomyopathy.

BACKGROUND: Information on genetic etiology of pediatric hypertrophic cardiomyopathy (HCM) rarely aids in risk stratification and prediction of disease onset. Little data exist on the association between genetic modifiers and phenotypic expression of myocardial performance, hampering an individual precision medicine approach. METHODS: Single-nucleotide polymorphism genotyping for six previously established disease risk alleles in the hypoxia-inducible factor-1α-vascular endothelial growth factor pathway was performed in a pediatric cohort with HCM. Findings were correlated with echocardiographic parameters of systolic and diastolic myocardial deformation measured by two-dimensional (2-D) speckle-tracking strain. RESULTS: Twenty-five children (6.1 ± 4.5 years; 69% male) with phenotypic and genotypic (60%) HCM were included. Out of six risk alleles tested, one, VEGF1 963GG, showed an association with reduced regional systolic and diastolic left ventricular (LV) myocardial deformation. Moreover, LV average and segmental systolic and diastolic strain and strain rate were significantly reduced, as assessed by the standardized difference, in patients harboring the risk allele. CONCLUSIONS: This is the first study to identify an association between a risk allele in the VEGF pathway and regional LV myocardial function, with the VEGF1 963GG allele associated with reduced LV systolic and diastolic myocardial performance. While studies are needed to link this information to adverse clinical outcomes, this knowledge may help in risk stratification and patient management in HCM. IMPACT: Risk allele in the VEGF gene impacts on LV myocardial deformation phenotype in children with HCM. LV 2-D strain is significantly reduced in patients with risk allele compared to non-risk allele patients within HCM patient groups. Describes that deficiencies in LV myocardial performance in children with HCM are associated with a previously identified risk allele in the angiogenic transcription factor VEGF. First study to identify an association between a risk allele in the VEGF pathway and regional LV myocardial deformation measured by 2-D strain in children with HCM.

Echocardiographic Assessment of Cardiac Function in Pediatric Survivors of Anthracycline-Treated Childhood Cancer.

BACKGROUND: Anthracycline-induced cardiotoxicity is a major cause of morbidity and mortality in childhood cancer survivors (CCSs). Echocardiographic myocardial strain imaging is recommended in adult patients with cancer, but its role in pediatric CCSs has not been well established. Aims of this study were to determine the prevalence of abnormalities in left ventricular strain in pediatric CCSs, to compare strain with other echocardiographic measurements and blood biomarkers, and to explore risk factors for reduced strain. METHODS: CCSs ≥3 years from their last anthracycline treatment were enrolled in this multicenter study and underwent a standardized functional echocardiogram and biomarker collection. Regression analysis was used to identify factors associated with longitudinal strain (LS). RESULTS: Five hundred forty-six pediatric CCSs were compared with 134 healthy controls. Abnormal left ventricular ejection fraction (<50%) and mean LS (Z score, <-2) was found in 0.8% and 7.7% of the CCSs, respectively. LS was significantly lower in CCSs than in controls, but the absolute difference was small (0.7%). Lower LS in CCSs was associated with older current age and higher body surface area. Sex, cumulative anthracycline dose, radiotherapy, and biomarkers were not independently associated with LS. Circumferential strain, diastolic parameters, and biomarkers were not significantly different in pediatric CCSs. CONCLUSIONS: Global systolic function and LS are only mildly reduced in pediatric CCSs, and most LS values are within normal range. This makes single LS measurements of limited added value in identifying CCSs at risk for cardiac dysfunction. The utility of strain imaging in the long-term follow-up of CCS remains to be demonstrated.

Association of Echocardiographic Parameters of Right Ventricular Remodeling and Myocardial Performance With Modified Task Force Criteria in Adolescents With Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: The usefulness of echocardiographic indices, including those already used by modified Task Force Criteria (mTFC), and others such as strain imaging, to identify arrhythmogenic right ventricular cardiomyopathy (ARVC) in adolescence is not well established. METHODS: Echocardiograms from 120 adolescents investigated for ARVC (13±4 years) were retrospectively analyzed. According to the mTFC, patients were classified into definite (n=38), borderline (n=39), or possible (n=43) ARVC. Results were compared with 35 healthy controls. mTFC echocardiographic parameters were analyzed, as well as comprehensive right ventricular (RV) and left ventricular assessment of function including parameters not included in mTFC such as pulsed-wave tissue Doppler and RV 2-dimensional speckle strain. RESULTS: mTFC parameters indexed for body surface area were significantly more abnormal in patients with possible, borderline, or definite ARVC compared with controls for parasternal long-axis view of the RV outflow tract. RV end-diastolic diameters were significantly larger in patients versus controls, a difference that increased with likelihood of ARVC. Left ventricular ejection fraction, tricuspid annular peak systolic excursion, and systolic and diastolic pulsed-wave tissue Doppler imaging indices were similar to controls for all groups. Average and segmental RV peak longitudinal systolic strain was significantly lower in patients with definite ARVC (-21±4%) and disease subgroups versus controls (-25±3%). Multivariable risk analysis showed that reduced RV strain was significantly associated with ARVC diagnosis and its likelihood (multivariable odds ratio [95% CI]=1.23 [1.1-1.37]; P<0.001) as was increased end-diastolic diameter at the apical third of the RV (multivariable odds ratio [95% CI]=1.51 [1.33-1.72]; P<0.001). CONCLUSIONS: mTFC echocardiographic criteria are significantly different between patients and controls and between the different diagnostic groups. However, in our cohort, current echocardiographic mTFC are not met by the majority of adolescent ARVC patients, particularly when indexed to body surface area. Measurement of RV apical dimensions and strain may increase the diagnostic yield of echocardiography for ARVC.

Prognostic Value of Serial Echocardiography in Hypoplastic Left Heart Syndrome.

BACKGROUND: Hypoplastic left heart syndrome (HLHS) carries a high mortality. The prognostic value of echocardiographic variables at presentation and the importance of serial data are poorly explored. METHODS AND RESULTS: We retrospectively analyzed longitudinal clinical and echocardiographic parameters of children with hypoplastic left heart syndrome. The primary outcome was time to death or transplant after stage-1 surgery, right censored at stage 3 surgery, accounting for sequential surgical procedures. Univariable and multivariable analysis identified risk factors for transplant or mortality. Time-dependent trends in echo parameters stratified by patient survival were explored using nonparametric methods. In total 67 children with hypoplastic left heart syndrome were included. The 10-week, 20-week, and 1-year survival proportions were 77.6% (66-86), 68.7% (56-78), and 54.1% (41-65), respectively. At presentation, multivariable analysis identified a thicker interventricular septum (hazard ratio [HR], 1.64; P=0.007) to be associated with increased risk for transplant/death, whereas higher tricuspid valve annular planar systolic excursion z score (HR, 0.61; P=0.003) was associated with reduced risk of mortality/transplant. After stage-1, higher body surface area-indexed right ventricular end-systolic area (HR, 1.52; P=0.02), lower fractional area change (HR, 1.18; P=0.01), and qualitatively decreased right ventricular function (HR, 2.55; P=0.08) were associated with increased risk of transplant-free mortality, censored at stage 3. Higher body surface area-indexed right ventricular end-diastolic area (HR, 0.76; P=0.04) and better tricuspid valve annular planar systolic excursion z score (HR, 0.49; P=0.01) were associated with lower mortality/transplant. During follow-up, right ventricular dilation, dysfunction, and tricuspid regurgitation improved in transplant-free survivors and worsened in those transplanted or who died. CONCLUSIONS: Conventional echocardiographic parameters at presentation and during follow-up are potential markers for transplant-free survival in children with hypoplastic left heart syndrome.

The aortic root does not dilate over time after replacement of the aortic valve and ascending aorta in patients with bicuspid or tricuspid aortic valves.

OBJECTIVE: Whether the aortopathy associated with bicuspid aortic valve (BAV) disease occurs secondary to genetic or hemodynamic factors remains controversial. In this article we describe the natural history of the aortic root in patients with bicuspid versus tricuspid aortic valves (TAVs) after replacement of the aortic valve and ascending aorta. METHODS: From 1990 to 2010, 406 patients (269 BAV, 137 TAV) underwent aortic valve and ascending aorta replacement at a single institution. Patients with aortic dissection, endocarditis, previous aortic surgery, or Marfan syndrome were excluded. All available follow-up imaging was reviewed. RESULTS: Mean imaging follow-up was 5.5 (±5.3) years. Of all patients, 66.5% had at least 1 aortic root measurement after the index operation. Baseline aortic diameter was comparable between groups. In patients with BAV, aortic root diameter increased at a clinically negligible rate over time (0.654 mm per year; 95% confidence interval, 0.291-1.016; P < .001), similar to patients with TAV (P = .92). Mean clinical follow-up was 8.1 (±5.4) years. During follow-up, 18 patients underwent reoperation, 89% for a degenerated bioprosthetic aortic valve. Only 1 patient underwent reoperation for a primary indication of aortic aneurysmal disease, 22 years after the index operation. There were no differences in cumulative incidence rates of aortic reoperation (P = .14) between patients with BAV and TAV. CONCLUSIONS: Mid-term imaging after aortic valve and ascending aorta replacement indicates that if the aortic root is not dilated at the time of surgery, the risk of enlargement over time is minimal, negating the need for prophylactic root replacement in patients with BAV or TAV.

Outcomes of Blalock-Taussig shunts in current era: A single center experience.

OBJECTIVES: Mortality associated with the modified Blalock-Taussig shunt (MBTS) remains high despite advanced perioperative management. This study was formulated to provide data on (1) current indications, (2) outcomes, and (3) factors affecting mortality and morbidity. DESIGN: A retrospective single center chart review identified 95 children (excluding hypoplastic left heart lesions) requiring a MBTS. Mortality and major morbidity were analyzed using the Kaplan Meier method and risk factor analysis using Cox's proportional hazard regression. RESULTS: Median age was 8 (0-126) days, weight 3.1(1.7-5.4) kg. Seventy-three percent were neonates, 58% duct dependent and 73% had single ventricle physiology. Ninety-seven percent had a sternotomy approach for shunt placement with 70% receiving a 3.5 mm graft. Mean graft index (shunt cross sectional area [mm2 ]/BSA [m2 ]) was 44.39 ± 8.04 and shunt size (mm) to body weight (kg) ratio 1.1 ± 0.2. Hospital mortality was 12%, with an interval mortality of 6%. Shunt thrombosis/stenosis occurred in 23% and pulmonary over circulation in 30%, while shunt reoperation was required in 12% and catheter intervention in 8% of the cohort. At 1-year, survival was 82.0% (95% CI [72.7%, 88.4%]), and survival free of major morbidity 61.4% (95% CI [50.7%, 70.5%]). Duct dependency predisposed to mortality (P = .01, HR 6.74 [1.54, 29.53]) and composite outcome (mortality and major morbidity) (P = .04, HR 2.15, CI [1.036, 4.466]) and higher graft index to mortality (P = .005, HR 1.07 [1.02, 1.12]). CONCLUSIONS: The commonest indication for a MBTS in the current era was single ventricle palliation. Morbidity and mortality was considerable, partly explained by the higher at risk population. Alternative methods to maintain pulmonary blood flow in place of a MBTS requires further investigation.

Reported electronic cigarette use among adolescents in the Niagara region of Ontario.

BACKGROUND: Use of electronic cigarettes (e-cigarettes) among adolescents has not been fully described, in particular their motivations for using them and factors associated with use. We sought to evaluate the frequency, motivations and associated factors for e-cigarette use among adolescents in Ontario. METHODS: We conducted a cross-sectional study in the Niagara region of Ontario, Canada, involving universal screening of students enrolled in grade 9 in co-operation with the Heart Niagara Inc. Healthy Heart Schools' Program (for the 2013-2014 school year). We used a questionnaire to assess cigarette, e-cigarette and other tobacco use, and self-rated health and stress. We assessed household income using 2011 Canadian census data by matching postal codes to census code. RESULTS: Of 3312 respondents, 2367 answered at least 1 question in the smoking section of the questionnaire (1274 of the 2367 respondents [53.8%] were male, with a mean [SD] age of 14.6 [0.5] yr) and 2292 answered the question about use of e-cigarettes. Most respondents to the questions about use of e-cigarettes (n = 1599, 69.8%) had heard of e-cigarettes, and 380 (23.8%) of these respondents had learned about them from a store sign or display. Use of e-cigarettes was reported by 238 (10.4%) students. Most of the respondents who reported using e-cigarettes (171, 71.9%) tried them because it was "cool/fun/new," whereas 14 (5.8%) reported using them for smoking reduction or cessation. Male sex, recent cigarette or other tobacco use, family members who smoke and friends who smoke were strongly associated with reported e-cigarette use. Reported use of e-cigarettes was associated with self-identified fair/poor health rating (odds ratio [OR] 1.9 (95% confidence interval [CI] 1.2-3.0), p < 0.001), high stress level (OR 1.7 (95% CI 1.1-2.7), p < 0.001) and lower mean (33.4 [8.4] × $1000 v. 36.1 [10.7] × $1000, p = 0.001) and median [interquartile range] (26.2 [5.6] × $1000 v. 28.1 [5.7] × $1000) household incomes. INTERPRETATION: Use of e-cigarettes is common among adolescents in the Niagara region and is associated with sociodemographic features. Engaging in seemingly exciting new behaviours appears to be a key motivating factor rather than smoking cessation.

Cost per responder associated with biologic therapies for Crohn's disease, psoriasis, and rheumatoid arthritis.

INTRODUCTION: Biologic therapies have demonstrated efficacy and safety in several chronic systemic disorders. The authors indirectly compared response rates and costs per responder associated with biologic treatments for moderate-to-severe Crohn's disease (CD), psoriasis (Ps), and/or rheumatoid arthritis (RA). METHODS: A systematic literature search was performed to identify phase 3 randomized controlled trials of biologics for CD (adalimumab, infliximab), Ps (adalimumab, etanercept, infliximab, ustekinumab 45 mg, ustekinumab 90 mg), or methotrexate-refractory RA (abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, tocilizumab). Food and Drug Administration-approved dosing schedules were evaluated. Published response rates were extracted, with response defined in CD, Ps, and RA as: ≥70-point reduction in CD Activity Index at 12 months; ≥75% improvement in Psoriasis Area and Severity Index at 3 months; and ≥50% improvement in American College of Rheumatology component scores at 6 months. Within each indication, mixed-treatment comparison meta-analyses were conducted to derive pooled estimates and 95% CIs of response rate difference versus placebo for each biologic, adjusting for cross-trial variation in control-arm response rates. Cost per responder was estimated for each biologic as projected per patient drug costs (2011 US$) divided by response rate difference. RESULTS: Altogether, 23 publications were selected. In CD, 12-month cost per responder was estimated at $116,291 (95% CI $71,637-208,348) for adalimumab and $125,169 (95% CI $60,532-267,101) for infliximab. Among biologics approved in Ps, 3-month cost per responder was lowest for adalimumab ($9,756; 95% CI $8,668-11,131), infliximab ($12,828; 95% CI $11,772-13,922), and ustekinumab 45 mg ($13,821; 95% CI $12,599-15,167). In RA, biologics with the lowest 6-month cost per responder were adalimumab ($27,853; 95% CI $19,284-40,270), etanercept ($29,140; 95% CI $14,170-61,030), and tocilizumab ($31,363; 95% CI $14,713-64,232). CONCLUSION: Meta-analyses of clinical trials found considerable variation in cost-effectiveness of biologic therapies for CD, Ps, and RA. These results may help determine biologic utilization in these chronic diseases.