Adult Congenital Heart Disease

Left ventricular strain and fibrosis in adults with repaired tetralogy of Fallot: A case-control study View Article de Alba CG, Khan A, Woods P, Broberg CS. Int J Cardiol. 2020 Sep 1:S0167-5273(20)33719-0. doi: 10.1016/j.ijcard.2020.08.092. Online ahead of print. PMID: 32882293 Take Home Points: Left ventricular dysfunction is an expected complication after rTOF and has significant prognostic implications. CMR can provide quantification of both myocardial strain analysis and diffuse fibrosis, both of which have associations with other clinical variables and outcomes: LVECV (left ventricular myocardial extracellular volume) was the only univariate predictor of arrhythmia. All 2D strains were significantly associated with hospitalization and death. However, no association was seen between global systolic strain and LV-ECV. The study suggests these metrics are reflective of different pathologic processes and related to different types of outcome. Commentary from Dr. Soha Romeih (Aswan, Egypt), section editor of ACHD Journal Watch:  The long-term follow-up of repaired tetralogy of Fallot (rTOF) is typically focused on RV systolic and diastolic function. However, the LV is also a factor contributing to decreased exercise capacity, ventricular arrhythmias, and mortality. A plausible explanation is that moderate to severe pulmonary insufficiency creates chronic RV volume load which drives RV dilation and increased RV wall stress, which in turn lead to LV dysfunction via ventricular-ventricular interactions. Myocardial extracellular volume (ECV), a surrogate of diffuse interstitial myocardial fibrosis, can be evaluated by T1 mapping. Increased myocardial fibrosis has been found in patients with TOF, even at a young age and has been associated with abnormal LV mechanics. In addition, CMR-based feature tracking (CMR-FT) assessment of myocardial strain can be used as a measure of both global and regional myocardial function. Its use in rTOF remains limited. Because both LV-ECV and strain measures reflect LV myocardial change, and because both have limited association with clinical endpoints, the study postulated that the two measures would be associated with one another. The primary aim of the study was to determine whether LV myocardial fibrosis measured by T1 mapping is associated with LV systolic strain measured by CMR-FT.  The secondary aim was to determine the association between LV systolic strain and LV-ECV with three major clinical outcomes: death, arrhythmia and hospitalization for heart failure. Patients and Methods: CMR studies from adults with rTOF and healthy subjects without known cardiovascular disease were retrospectively reanalyzed.  Strain analysis was done using the tissue tracking algorithm in Circle Cardiovascular Imaging Software (Version 5.6.8 Calgary, Canada). LV-ECV was quantified using a single short axis Look-Locker sequence at the midmyocardium, for which signal intensity vs. time curves were plotted for myocardium and blood pool before and several time points up to 25 min after contrast administration. New atrial arrhythmia was defined as a sustained atrial arrhythmia, either symptomatic or requiring treatment. Ventricular arrhythmia was defined as non-sustained ventricular tachycardia lasting 30 beats, or any symptomatic ventricular arrhythmia requiring treatment. Non-elective hospitalizations for heart failure symptoms or elevated BNP requiring diuresis were considered. Results: The initial study cohort consisted of 52 rTOF subjects. Upon review, four rTOF subjects did not have adequate quality cine imaging in all views, either because of respiratory artifact or gating issues, to make accurate strain quantifications and were not included.  The remaining 48 rTOF subjects constituted our patient cohort (age 40.5, SD = 14.3 years, 42% female) with 20 controls (age 39.4, SD = 11.9, 45% female). Group comparisons are presented in Table 1. As expected, the groups also differed by LV systolic volume, LV ejection fraction, left atrial volume, and RV size and function. Global circumferential strain (GCS), both 2 dimensional (2D) and 3 dimensional (3D) were lower in rTOF subjects (p ≤0.0001 for both, Table 1). Global longitudinal strain (GLS) both by 2D and 3D were also significantly lower in rTOF subjects (p ≤0.0001 for both). Global 2D radial strain (GRS) was lower in rTOF subjects compared to controls (Table 1). LVEF and LVESV were both significantly associated with all global (2D and 3D) peak systolic strain values. No significant association was seen between strain and right ventricular volumetric parameters. There was a weak association between all 2D strain parameters and RVEF, however this was not significant after adjusting for multiple comparisons. There was no association between global systolic strain and LV-ECV. Kaplan-Meier plots for arrhythmia free survival and death (Figure. 1), for both LV-ECV and GLS are shown. By Cox-regression analysis, LVECV was the only univariate predictor of arrhythmia. All 2D strains were significantly associated with hospitalization and death (univariate). LV-ECV was also a significant univariate predictor of both hospitalization and death. Based on limited multivariate models, the only consistent independent predictor of arrhythmia was LV-ECV (HR=1.198, 95% CI 1.04–1.38, p=0.013). GLS was the only consistent multivariate predictor of hospitalization (HR = 1.48, 95% CI 1.11–1.96, p = 0.007) and of death (HR = 1.63, 95% CI 1.16–2.30, p = 0.005). Discussion: ECV and myocardial strain have gained wide interest in the last decade as tools for myocardial assessment. Our study confirms that both LV-ECV and global systolic strain are abnormal compared to controls and are associated with cardiac chamber size and function and clinical outcome. Previous studies have shown associations between these measures and clinical events such as arrhythmias, LV systolic and diastolic dysfunction and death, though with some mixed results. Therefore, strain and fibrosis both appear to demonstrate different myocardial characteristics that may both play a role in the natural history of rTOF. This study explored the relationship between fibrosis and strain quantified from the same imaging examination. It included a wide range of strain parameters and found no association between these two types of metrics. Our results differ from previous investigators who found that T1-derived markers for myocardial fibrosis in rTOF patients were moderately related to peak LV radial strain and weakly associated to circumferential strain. Interestingly, that study was performed in a younger population than ours (mean age 26 ± 11 years) who had a mean lower LV-ECV overall (24.5 ± 5.1). The varying findings may also reflect different strain analysis algorithms inherent in different commercially available analysis modules. Conclusion: While both LV strain abnormalities and fibrosis are present in rTOF, they are associated with different types of clinical outcome, and not to each other. The findings suggest that these measures reflect different long-term adverse adaptations to abnormal hemodynamics. Limitations: Strain quantification methods and algorithms differ between software vendors, and strain values between echo and CMR are not comparable. The study is small with low number of outcomes. A larger cohort would allow stronger confirmation of the findings. Multivariate regression was limited given the low number of clinical outcomes.

Comparison of risk stratification models for pregnancy in congenital heart disease View Article Denayer N, Troost E, Santens B, De Meester P, Roggen L, Moons P, Van Calsteren K, Budts W, Van De Bruaene A. Int J Cardiol. 2020 Sep 12:S0167-5273(20)33814-6. doi: 10.1016/j.ijcard.2020.09.033. Online ahead of print. PMID: 32931856 Take Home Points: There are several risk stratification tools which are utilised to ‘predict’ adverse outcomes in women with congenital heart disease who become pregnant. There are 4 commonly employed maternal risk predictive tools – CARPREG, CARPREG II, ZAHARA and the modified WHO score. This study randomly selected 100 women and for each woman, the 4 risk prediction tools were calculated and summarised in a weighted average risk for each stratification model. To evaluate accuracy of each model, the weighted average risk was plotted against the actual observed number of “cardiac events” as defined in the respective risk models. Maternal adverse events occurred in 8% of the study population – all in patients with at least moderately complex CHD. All the risk models over-estimated maternal cardiac risk but in this selected cohort, the ZAHARA risk model appeared to be a closer reflection of maternal risk. Commentary from Dr. Damien Cullington (Liverpool, UK), section editor of ACHD Journal Watch:  Neil’s Bohr rightly pointed out: “Prediction is very difficult, especially if it’s about the future” and predicting risks to women with CHD during pregnancy is no different. The CARPREG, CARPREG II, ZAHARA and modified WHO (mWHO) score are the main risk predictive scores employed to estimate risk in pregnant women with CHD – the most recently updated ESC guidelines for the management of cardiovascular disorders during pregnancy advocate the use of the mWHO score. Head-to-head comparison is challenging “since the different models have been constructed in different patient populations with different outcome measures”. This study sought to compare the 4 scores against each other to assess which predicts outcome best. The characteristics of the patient cohort (n=100) are shown in Table 1. Over half of patients were primigravida (n=52) and the mean maternal age was 30.4 ± 3.7 yrs. 98% had a biventricular circulation. The four commonest CHD conditions were VSD (n=34), coarctation (n=16), TOF (n=15) and ASD (n=14). Pre-pregnancy, 97% had no symptoms of heart failure. Only 15% of the cohort were taking medication pre-pregnancy. Outcomes The actual rate of maternal cardiac complications was 8% - (Tables 2a and 2b). For each of the 4 models, a composite risk was calculated. The predictive accuracy for each risk model is shown in Table 3. There was one sudden cardiac death in a patient with Marfan syndrome 4 days post-partum but aside from this case, all CV complications occurred in patients with at least moderate complexity CHD – (4 TOF, 2 atrial switch and 1 Fontan). No complications were seen in patients with simple CHD lesions. Conclusions All models tended to over-estimate risk but ZAHARA was the closest in making an accurate prediction of CV event for this selected dataset. Work continues to refine how we predict risk. The authors suggest that work should also be focused on developing a risk score for patients referred and managed in cardio-obstetric centres.  

Outcomes of heart transplantation in adult congenital heart disease with prior intracardiac repair View Article Kainuma A, Sanchez J, Ning Y, Kurlansky PA, Axsom K, Farr M, Sayer G, Uriel N, Takayama H, Naka Y, Takeda K. Ann Thorac Surg. 2020 Sep 16:S0003-4975(20)31478-8. doi: 10.1016/j.athoracsur.2020.06.116. Online ahead of print. PMID: 32949612 Take Home Points: Operative risk in orthotopic heart transplantation is higher in ACHD patients with prior intracardiac repair as compared to propensity matched non-ACHD patients for both: 30-day mortality (8.2% vs. 3.9%, p=0.004) perioperative need of dialysis (22.7% vs. 13.3%, p<0.001) 10-year survival, however, is equivalent (ACHD 66.0% vs. control 64.1%, log-rank p=0.353) This data supports ACHD patients being listing for heart transplantation. Earlier listing of ACHD patients prior to the onset of end-organ dysfunction, and detailed preoperative planning with modern techniques including 3D modelling, may help reduce early surgical mortality. Commentary by Dr. Timothy Roberts (Melbourne, Australia), section editor of ACHD Journal Watch:  The proportion of cardiac transplants performed in ACHD patients remains low, despite a greater number requiring such intervention as survival improves and more patients face end stage heart failure. Data from earlier this century has demonstrated increased operative mortality, however more contemporary outcomes are lacking. This current paper is a retrospective analysis of ACHD patients with prior intracardiac repair undergoing orthotopic heart transplantation (OHT) between 2008 – 2019 using the United Network for Organ Sharing database. Adult (age > 17) cardiac transplant recipients who had a history of prior sternotomy were divided into ACHD and non-ACHD (control) groups. 792 ACHD and 8385 non-ACHD patients were included for propensity score matching. Clinical (body mass index, diabetes, smoking, history of malignancy, history of cerebrovascular disease, creatinine, dialysis, total bilirubin, need for transfusion, extracorporeal membrane oxygenation, intra-aortic balloon pump, ventricular assist device, total times on waiting list, ventilator dependent, inotrope dependent, pulmonary capillary wedge pressure, ischemic time, functional status, intensive care unit stay) and demographic (age, gender) characteristics were used for propensity scoring. ACHD and control groups were matched 1:1; 486 (5.8%) cases in control and 486 (61.4%) in ACHD were matched successfully. Table 1 shows ACHD and non-ACHD recipient group characteristics, before propensity score matching. At the time of transplant ACHD patients were younger, had a higher proportion of females, a higher total bilirubin at transplant, had spent more time on the waiting list, and were more inotrope dependent. Table 2 illustrates 30-day post-transplant outcomes for ACHD and non-ACHD recipients after propensity score matching. ACHD patients had an increased need of dialysis, longer length of stay, and greater 30-day mortality. Risk factors for 30-day mortality in the ACHD group were BMI ( 25 kg/m2), history of cerebrovascular disease, dialysis after listing, total bilirubin ( 1.2 mg/dl), ischaemic time ( 4 hours), and donor age ( 50 years). The need for post-transplant dialysis had a profound impact on 10-year mortality in both ACHD (70.1% vs 45.1%, p<0.001) and non-ACHD (60.0% vs 28.4%, p<0.001) groups. Findings from the current study again identify higher operative mortality. Likely explanations for this include the complex anatomical variation in ACHD patients, multiple prior palliative or corrective surgeries, and extensive reconstruction requirements with resultant longer ischemic time and increased bleeding risk. The authors found pretransplant end-organ dysfunction and longer ischemic times were independent predictors of mortality. Earlier listing of ACHD patients prior to the onset of end-organ dysfunction, and detailed preoperative planning with modern techniques including 3D modelling may be beneficial.