The role of cardiopulmonary exercise testing (CPET) in predicting mortality and morbidity in people with congenital heart disease: a systematic review and meta-analysis (Protocol)

This is the final version. Available from BMC via the DOI in this record.Background Numerous studies have measured the prognostic associations between cardiorespiratory fitness and patient outcomes in congenital heart disease, but no systematic review has assessed these associations for all types of congenital heart disease. It is therefore a timely opportunity to syntheses all available data using a systematic review methodology. The aim of this study is to detail the protocol for a systematic review and meta-analysis. Objectives Within this paper we have developed a protocol for a prognostic factors systematic review and meta-analysis, to assess the role of cardiopulmonary exercise testing/cardiorespiratory fitness, in the prognosis of mortality and morbidity in congenital heart disease. Methods We have outlined, in detail, the process for this systematic review using the latest accepted methodological guidelines for prognostic factors research, such as the PICOTS system, CHARMS-PF data extraction, QUIPS risk of bias assessments and the prognostic GRADE guidelines (see list of abbreviations). Conclusion The implications of this review will aid future treatments, interventions and individual patient risk prediction. The publication of this protocol aims to improve scientific rigour by ensuring transparency in the systematic review and meta-analysis process.Canon Medical Systems UK Ltd.University of ExeterQUEX instituteMedical Research Counci

Outcomes following repair of anomalous coronary artery from the pulmonary artery in infants: results from a procedure-based national database

BACKGROUND: Anomalous coronary artery from the pulmonary artery (ACAPA) is a very rare congenital anomaly that often occurs during infancy. Patients can present in a critical condition. METHODS: We analysed procedure-related data from a national audit database for the period 2000-2013. RESULTS: A total of 120 patients 30 days) were available in 102 patients and the mean follow-up time was 4.7 years. The 30-day overall mortality was 1.9%, higher for neonates (16.7% vs 1%, p=0.1) and after postoperative extracorporeal membrane oxygenation (ECMO) (20% vs 1%, p=0.09). At 10 years the survival estimate is 95.1%, freedom from coronary and mitral reintervention being 95.9% and 91.2%, respectively. Use of postoperative ECMO was a risk factor for long-term mortality (p<0.001). Risk factors for coronary reintervention were age under 30 days (p=0.06) and the need for postoperative ECMO (p=0.02). Age under 30 days (p=0.002) was a risk factor for mitral reintervention. CONCLUSIONS: To our knowledge this is the largest series to date. These preliminary national results show that early outcomes are good and medium-term attrition acceptable. Poor outcomes are correlated with early presentation, also with the need for postoperative circulatory support

The Role of Speckle Tracking Echocardiography in the Evaluation of Common Inherited Cardiomyopathies in Children and Adolescents: A Systematic Review

This is the final version. Available on open access from MDPI via the DOI in this recordData Availability Statement: Data available on request.Speckle tracking echocardiography (STE) has gained importance in the evaluation of adult inherited cardiomyopathies, but its utility in children is not well characterized. We conducted a systematic review to evaluate the role of STE in pediatric inherited cardiomyopathies. PubMed, EMBASE, Web of Science, Scopus, CENTRAL and CINAHL databases were searched up to May 2020, for terms related to inherited cardiomyopathies and STE. Included were dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), left ventricular non-compaction (LVNC) and arrhythmogenic cardiomyopathy (ACM). A total of 14 cohorts were identified, of which six were in DCM, four in HCM, three in LVNC and one in ACM. The most commonly reported STE measurements were left ventricular longitudinal strain (Sl), circumferential strain (Sc), radial strain (Sr) and rotation/torsion/twist. Sl, Sc and were abnormal in all DCM and LVNC cohorts, but not in all HCM. Apical rotation and twist/torsion were increased in HCM, and decreased in LVNC. Abnormal STE parameters were reported even in cohorts with normal non-STE systolic/diastolic measurements. STE in childhood cardiomyopathies can detect early changes which may not be associated with changes in cardiac function detectable by non-STE methods. Longitudinal and circumferential strain should be introduced in the cardiomyopathy echocardiography protocol, reflecting current practice in adults.Medical Research Council (MRC)Majlis Amanah Rakyat (MARA)University of ExeterCanon Medical Systems UK Ltd

The Role of Speckle-Tracking Echocardiography in Predicting Mortality and Morbidity in Patients With Congenital Heart Disease: A Systematic Review and Meta-analysis

This is the final version. Available on open access from Elsevier via the DOI in this recordData Availability Statement: The data underlying this article will be shared on reasonable request to the corresponding authorBACKGROUND: Speckle-tracking echocardiography (STE) is now routinely included in cardiac evaluations, but its role in predicting mortality and morbidity in congenital heart disease (CHD) is not well described. We conducted a systematic review to evaluate the prognostic value of STE in patients with CHD. METHODS: The EMBASE, Medline, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception to January 2023 for terms related to all CHD, STE, and prognosis. Meta-analysis of association of right ventricle and left ventricle strain (RV Sl and LV Sl, respectively) with major adverse cardiovascular events (MACEs) was performed in atrial switch transposition of the great arteries (asTGA)/congenitally corrected TGA (ccTGA), tetralogy of Fallot (ToF), and congenital aortic stenosis (cAS)/bicuspid aortic valve (BAV). P-value combination analysis was additionally performed for all CHD groups. RESULTS: A total of 33 studies (30 cohorts, n = 8,619 patients, children, and adults) were included. Meta-analysis showed the following parameters as being associated with MACE: RV Sl in asTGA/ccTGA (hazard ratio [HR] = 1.1/%; CI, [1.03; 1.18]), RV Sl and LV Sl in ToF (HR = 1.14/%; CI, [1.03; 1.26] and HR = 1.14/%; CI, [1.08; 1.2], respectively), and LV Sl in cAS/BAV (HR = 1.19/%; CI, [1.15; 1.23]). The RV Sl and strain rate were associated with outcomes also in single ventricle/hypoplastic left heart syndrome (at all palliation stages except before Norwood stage 1) and LV Sl in Ebstein's anomaly. CONCLUSIONS: This systematic review and meta-analysis showed that biventricular strain and strain rate were associated with outcomes in a variety of CHD, highlighting the need for updated recommendations on the use of STE in the current guidelines, specific to disease types

Factors associated with unplanned reinterventions and their relation to early mortality after pediatric cardiac surgery

Objective: Unplanned reintervention (uRE) is used as an indicator of patient morbidity and quality of care in pediatric cardiac surgery. We investigated associated factors and early mortality after uREs. / Methods: Morbidity data were prospectively collected in 5 UK centers between 2015 and 2017; uRE included surgical cardiac, interventional transcatheter cardiac, permanent pacemaker, and diaphragm plication procedures. Mortality (30-day and 6-month) in uRE/no-uRE patients was reported before and after matching. Predicted 30-day mortality was calculated using the Partial Risk Adjustment in Surgery score. / Results: A total of 3090 procedures (2861 patients) were included (median age, 228 days). There were 146 uREs, resulting in an uRE rate of 4.7%. Partial Risk Adjustment in Surgery score, 30-day mortality and 6-month mortality in uRE and no-uRE groups were 2.4% versus 1.3%, 8.9% versus 1%, and 17.1% versus 2.4%, respectively. After matching, mortality at 6 months remained higher in uRE compared with no-uRE (12.2% vs 1.4%; P = .02; 74 pairs). In the uRE group, 21 out of 25 deaths at 6 months occurred when at least 1 additional postoperative complication was present. In multivariable analysis, neonatal age (P = .002), low weight (P = .009), univentricular heart (P < .001), and arterial shunt (P < .001) were associated with increased risk of uRE, but Partial Risk Adjustment in Surgery score was not (only in univariable analysis). / Conclusions: uREs are a relatively frequent complication after pediatric cardiac surgery and are associated with some patient characteristics, but not the Partial Risk Adjustment in Surgery risk score. Early mortality was higher after uRE, independent of preoperative factors, but linked to other postoperative complications

Investigating the Accuracy of Quantitative Echocardiographic-Modified Task Force Criteria for Arrhythmogenic Ventricular Cardiomyopathy in Adolescent Male Elite Athletes

This is the final version. Available on open access from Springer via the DOI in this recordAthlete preparticipation screening focuses on preventing sudden cardiac death (SCD) by detecting diseases such as arrhythmogenic ventricular cardiomyopathy (AVC), which affects primarily the right ventricular myocardium. Diagnosis may be obscured by physiological remodeling of the athlete heart. Healthy athletes may meet the 2010 Task Force Criteria right ventricular outflow tract (RVOT) dimension cut-offs, questioning the suitability of the modified Task Force Criteria (mTFC) in adolescent athletes. In this study, 67 male adolescent footballers undergoing preparticipation screening were reviewed. All athletes underwent a screening for resting ECG and echocardiogram according to the English FA protocol, as well as cardiopulmonary exercise testing, stress ECG, and exercise echocardiography. Athletes' right ventricular outflow tract (RVOT) that met the major AVC diagnostic criteria for dilatation were identified. Of 67 evaluated athletes, 7 had RVOT dilatation that met the major criteria, all in the long axis parasternal view measurement. All had normal right ventricular systolic function, including normal free-wall longitudinal strain (ranging from - 21.5 to - 32.7%). Left ventricular ejection fraction ranged from 52 to 67%, without evidence of structural changes. Resting ECGs and cardiopulmonary exercise tests were normal in all individuals. In a series of healthy athletes meeting the major AVC diagnostic criteria for RVOT dilatation, none had any other pathological changes on a detailed screening including ECG, exercise testing, and echocardiography. This report highlights that current AVC echocardiographic diagnosis criteria have limitations in this population.National Institute for Health Research (NIHR)Medical Research Council (MRC

The role of cardiopulmonary exercise testing in predicting mortality and morbidity in people with congenital heart disease: a systematic review and meta-analysis

This is the final version. Available on open access from Oxford University Press via the DOI in this recordBackground: The role of cardiopulmonary exercise testing (CPET) in predicting major adverse cardiovascular events (MACE) in people with congenital heart disease (ConHD) is unknown. Design: A systematic review with meta-analysis was conducted to report the associations between CPET parameters and MACE in people with ConHD. Methods: Electronic databases were systematically searched on the 30th of April 2020 for eligible publications. Two authors independently screened publications for inclusion, extracted study data, and performed risk of bias assessment. Primary meta-analysis pooled univariate hazard ratios (HR) across studies. Results: A total of 34 studies (18,335 participants; 26.2 ± 10.1 years; 54% ± 16% male) were pooled into a meta-analysis. More than 20 different CPET prognostic factors were reported across 6 ConHD types. Of the 34 studies included in the meta-analysis, 10 (29%), 23 (68%), and 1 (3%) were judged as a low, medium, and high risk of bias, respectively. Primary univariate meta-analysis showed consistent evidence that improved peak and submaximal CPET measures are associated with a reduce risk of MACE. This association was supported by a secondary meta-analysis of multivariate estimates and individual studies that could not be numerically pooled. Conclusion: Various maximal and submaximal CPET measures are prognostic of MACE across a variety of ConHD diagnoses. Further well conducted prospective multicentre cohort studies are needed to confirm these findings.Canon Medical Systems UK Ltd.University of ExeterQUEX instituteMedical Research Council (MRC

The use of 2-D speckle tracking echocardiography in assessing adolescent athletes with left ventricular hypertrabeculation meeting the criteria for left ventricular non-compaction cardiomyopathy.

This is the final version. Available from Elsevier via the DOI in this record. BACKGROUND: Current echocardiographic criteria cannot accurately differentiate exercise induced left ventricular (LV) hypertrabeculation in athletes from LV non-compaction cardiomyopathy (LVNC). This study aims to evaluate the role of speckle tracking echocardiography (STE) in characterising LV myocardial mechanics in healthy adolescent athletes with and without LVNC echocardiographic criteria. METHODS: Adolescent athletes evaluated at three sports academies between 2014 and 2019 were considered for this observational study. Those meeting the Jenni criteria for LVNC (end-systolic non-compacted/compacted myocardium ratio > 2 in any short axis segment) were considered LVNC+ and the rest LVNC-. Peak systolic LV longitudinal strain (Sl), circumferential strain (Sc), rotation (rot), corresponding strain rates (SRl/c) and segmental values were calculated and compared using a non-inferiority approach. RESULTS: A total of 417 participants were included, mean age 14.5 ± 1.7 years, of which 6.5% were LVNC+ (n = 27). None of the athletes showed any additional LVNC clinical criteria. All average Sl, SRl Sc, SRc and rot values were no worse in the LVNC+ group compared to LVNC- (p values range 0.0003-0.06), apart from apical SRc (p = 0.2). All 54 segmental measurements (Sl/Sc SRl/SRc and rot) had numerically comparable means in both LVNC+ and LVNC-, of which 69% were also statistically non-inferior. CONCLUSIONS: Among healthy adolescent athletes, 6.5% met the echocardiographic criteria for LVNC, but showed normal LV STE parameters, in contrast to available data on paediatric LVNC describing abnormal myocardial function. STE could better characterise the myocardial mechanics of athletes with LV hypertrabeculation, thus allowing the transition from structural to functional LVNC diagnosis, especially in suspected physiological remodelling.Medical Research CouncilEuropean Society of Cardiolog

The use of 2-D speckle tracking echocardiography in differentiating healthy adolescent athletes with right ventricular outflow tract dilation from patients with arrhythmogenic cardiomyopathy

This is the final version. Available on open access from Elsevier via the DOI in this recordAIMS: Echocardiographic assessment of adolescent athletes for arrhythmogenic cardiomyopathy (ACM) can be challenging owing to right ventricular (RV) exercise-related remodelling, particularly RV outflow tract (RVOT) dilation. The aim of this study is to evaluate the role of RV 2-D speckle tracking echocardiography (STE) in comparing healthy adolescent athletes with and without RVOT dilation to patients with ACM. METHODS AND RESULTS: A total of 391 adolescent athletes, mean age 14.5 ± 1.7 years, evaluated at three sports academies between 2014 and 2019 were included, and compared to previously reported ACM patients (n = 38 definite and n = 39 borderline). Peak systolic RV free wall (RVFW-Sl), global and segmental strain (Sl), and corresponding strain rates (SRl) were calculated. The participants meeting the major modified Task Force Criteria (mTFC) for RVOT dilation were defined as mTFC+ (n = 58, 14.8%), and the rest as mTFC- (n = 333, 85.2%). Mean RVFW-Sl was -27.6 ± 3.4% overall, -28.2 ± 4.1% in the mTFC+ group and - 27.5 ± 3.3% in the mTFC- group. mTFC+ athletes had normal RV-FW-Sl when compared to definite (-29% vs -19%, p < 0.001) and borderline ACM (-29% vs -21%, p < 0.001) cohorts. In addition, all mean global and regional Sl and SRl values were no worse in the mTFC+ group compared to the mTFC- (p values range < 0.0001 to 0.1, inferiority margin of 2% and 0.1 s-1 respectively). CONCLUSIONS: In athletes with RVOT dilation meeting the major mTFC, STE evaluation of the RV can demostrate normal function and differentiate physiological remodelling from pathological changes found in ACM, improving screening in grey-area cases.Medical Research Council (MRC

The use of 2-D speckle tracking echocardiography in differentiating healthy adolescent athletes with right ventricular outflow tract dilation from patients with arrhythmogenic cardiomyopathy

Aims: Echocardiographic assessment of adolescent athletes for arrhythmogenic cardiomyopathy (ACM) can be challenging owing to right ventricular (RV) exercise-related remodelling, particularly RV outflow tract (RVOT) dilation. The aim of this study is to evaluate the role of RV 2-D speckle tracking echocardiography (STE) in comparing healthy adolescent athletes with and without RVOT dilation to patients with ACM. Methods and results: A total of 391 adolescent athletes, mean age 14.5 ± 1.7 years, evaluated at three sports academies between 2014 and 2019 were included, and compared to previously reported ACM patients (n = 38 definite and n = 39 borderline). Peak systolic RV free wall (RVFW-Sl), global and segmental strain (Sl), and corresponding strain rates (SRl) were calculated. The participants meeting the major modified Task Force Criteria (mTFC) for RVOT dilation were defined as mTFC+ (n = 58, 14.8%), and the rest as mTFC- (n = 333, 85.2%). Mean RVFW-Sl was −27.6 ± 3.4% overall, −28.2 ± 4.1% in the mTFC+ group and − 27.5 ± 3.3% in the mTFC- group. mTFC+ athletes had normal RV-FW-Sl when compared to definite (−29% vs −19%, p < 0.001) and borderline ACM (−29% vs −21%, p < 0.001) cohorts. In addition, all mean global and regional Sl and SRl values were no worse in the mTFC+ group compared to the mTFC- (p values range < 0.0001 to 0.1, inferiority margin of 2% and 0.1 s−1 respectively). Conclusions: In athletes with RVOT dilation meeting the major mTFC, STE evaluation of the RV can demostrate normal function and differentiate physiological remodelling from pathological changes found in ACM, improving screening in grey-area cases