Adult Congenital Heart Disease

Predicting Survival in Repaired Tetralogy of Fallot: A Lesion-Specific and Personalized Approach. Ghonim S, Gatzoulis MA, Ernst S, Li W, Moon JC, Smith GC, Heng EL, Keegan J, Ho SY, McCarthy KP, Shore DF, Uebing A, Kempny A, Alpendurada F, Diller GP, Dimopoulos K, Pennell DJ, Babu-Narayan SV.JACC Cardiovasc Imaging. 2022 Feb;15(2):257-268. doi: 10.1016/j.jcmg.2021.07.026. Epub 2021 Oct 13.PMID: 34656466   Take Home Points: No single risk factor adequately predicts mortality and ventricular arrhythmias in rTOF In patients with a repaired TOF, the following factors emerged as independent on multivariate analysis: RVLGE – HR 11.4 (95%CI 2.7-4.8, p=0.001) – first study to show this LVLGE RVEF <35% LVEF <35% BNP levels >127ng/L Peak VO2 <17ml/kg/min Sustained atrial arrhythmia Age 50 or greater The weighted risk score described in this paper delineates the high-risk categories for mortality and for ventricular arrhythmias     Commentary from Dr. Blanche Cupido (Cape Town, South Africa), chief section editor of ACHD Journal Watch: The growing population with repaired Tetralogy of Fallot (rTOF) frequently experience late consequences like premature death (including SCD), and ventricular arrhythmias. The evidence base to direct accurate risk stratification in this group remains inadequate. Observational studies have implicated a number of haemodynamic, electrophysiological and structural factors, though no single factor in isolation has been able to predict VT or SCD with certainty. The challenge remains balancing the risk of VT/SCD against the complications of inappropriate shocks with ICD implantation. This prospective cohort aimed to assess the prognostic value of late gadolinium enhancement (LGE) on CMR (non-invasive assessment of VT substrate) and to devise a weighted-risk score for the assessment of SCD and VT using all the proven independent risk factors.   Consecutive patients with rTOF > age 16 were enrolled prospectively at a number of academic centers in London between 2002 and 2019 for CMR LGE testing in addition to standard care (clinical examination, ECG, BNP, echo, CPET). Holter monitoring was only done if clinically indicated. Patients with contra-indications to CMR and gadolinium were excluded. In addition to the usual CMR protocol, LGE imaging was obtained for LV and RV. Two experienced operators were blinded in their assessments.   The primary endpoints were all cause mortality. Secondary endpoints included Ventricular arrhythmias (VA) including SCD, resuscitated ventricular arrhythmias, and clinically sustained VT (either sustained >30s, or requiring cardioversion).   A total of 550 patients with CMR LGE were enrolled. Fifty-seven percent were male. The mean duration of follow-up was 6.4 years – a total of 3512 patient-years. RV LGE was seen at all the surgical sites in all patients. 98% seen in the RVOT and 100% at VSD patch sites. LGE was also found in RV trabeculations and the RV moderator band in ±32% of patients. Non-apical LV LGE only seen in 7% (n=41 – infarct-related in 8, papillary muscle/trabeculations in 20 and rest related to VSD patch).   Twenty-seven deaths were recorded during the follow-up period – 13 SCD, 12 due to heart failure, 2 non-cardiac deaths. In addition to a number of univariate analysis factors, in keeping with past observational studies, RVLGE score of 5 or greater emerged as a predictor for higher mortality and ventricular arrhythmias. Figure 2 (above) illustrates that RVLGE predicted both mortality and ventricular arrhythmias. Of note, Non-sustained VT (NSVT), previous palliative shunt, ventriculotomy, QRS duration >180ms and RV restrictive physiology were not univariate predictors of mortality.   On multivariate analysis, the following remained independent predictors of mortality:   RVLGE – HR 11.4 (95%CI 2.7-4.8, p=0.001) LVLGE RVEF <35% LVEF <35% BNP levels >127ng/L Peak VO2 <17ml/kg/min Sustained atrial arrhythmia Age 50 or greater     These factors were weighted and included in the development of the risk score depicted in Figure 3 above. A risk score of >51 had a 93% specificity and 51% sensitivity for mortality at one year. The high risk group portended a mortality rate of 4.4% per year. For every one point increase in the risk-score, there was an associated increase 7% risk of death (HR 1.07). Compared to a number of other existing risk models, this one performed better overall (AUC 0.87, 95% CI 0.78-0.95, p<0.001).   In terms of secondary outcomes – Ventricular Arrhythmias: Twenty-nine patients reached the ventricular arrhythmia composite endpoint. RVLGE (fig 2 above) was predictive of ventricular arrhythmias. Other independent risk factors included: Restrictive RV physiology but only when associated with RV dilatation.     Similarly, the independent risk factors were devised into a risk score. For ventricular arrhythmias, a value of >40 demarcated the high-risk category with an annual rate of 3.7% events per year.    

Prognostic Implications of Bicuspid and Tricuspid Aortic Valve Phenotype on Progression of Moderate Aortic Stenosis and Ascending Aorta Dilatation. Chew NWS, Phua K, Ho YJ, Zhang A, Lin N, Ngiam JN, Lau YX, Teo VXY, Sia CH, Loh PH, Kuntjoro I, Wong RCC, Lee CH, Tan HC, Yeo TC, Kong WKF, Poh KK.Am J Cardiol. 2021 Dec 15;161:76-83. doi: 10.1016/j.amjcard.2021.08.050. Epub 2021 Oct 6.PMID: 34627597   Take Home Points: Compared to patients with tricuspid aortic valves with a comparable degree of stenosis, patients with bicuspid aortic valve stenosis are younger and have larger aortic dimensions. Over time, these patients have a comparable rate of progression of hemodynamics and aortic dimensions. There was no significant difference in the rate of all-cause mortality, heart failure admission, or aortic valve replacement between these two groups. Commentary from Dr. MC Leong (Kuala Lumpur), section editor of ACHD Journal Watch: Bicuspid aortic valve (BAV) is the commonest congenital valvular abnormality. It is associated with aortic valve stenosis, incompetency and importantly aortopathy, manifested by dilatation of the ascending thoracic aorta. Progressive dilatation of the ascending aorta may lead to dissection of the aorta unless timely aortic root dilatation is carried out. This study examined the differences in the anatomic and hemodynamic progression of patients with moderate bicuspid aortic stenosis and its rate of ascending aortic dilatation using patients with tricuspid aortic valve (TAV) as control.   This was a single-center, retrospective study involving 288 patients (mean age: 67 ± 15 years, male: 46.5%) with at least 1 year of echocardiographic follow-up. The study defined moderate aortic stenosis (AS) as an aortic valve area of 1.0-1.5cm2while severe AS was defined as an aortic valve area < 1.0cm2. Meanwhile, rapid ascending aortic (AA) progression was defined as AA dilatation rate ≥+0.50 mm/year. All measurements were made on echocardiogram.   Baseline demographics were shown in Table 1. At baseline, no difference was seen in the severity of the aortic valve stenosis between the BAV and TAV groups. Patients in the BAV groups were younger and had larger aortic root dimensions at baseline. Over the period of 1 year, the progression of the aortic valve stenosis and aortic dimensions were comparable between the groups (Table 2). After 1 year, hemodynamics changes were again, not significantly different between the groups. However, there was a trend toward a higher prevalence of rapid progressors of AA dilatation in the BAV group (p= 0.099).       The mean follow-up duration was 58.2 ± 40.7 months. During the follow-up period, the authors found a trend toward a higher incidence of aortic valve replacement in the BAV group (27.5%) compared with the TAV group (17.3%, p = 0.053). Those who progressed to severe AS were of younger and were more likely to require aortic valve replacement (Table 4). BAV was not found to be an independent predictor of all-cause mortality, heart failure admission, or aortic valve replacement in multivariate analyses. There were initially a lower freedom of aortic valve replacement and a higher mortality rate in the BAV group, in the Kaplan-Meier curve analyses. However, in the adjusted Kaplan-Meier curves, there were no statistically significant differences in heart failure admissions, aortic valve replacement, or all-cause mortality between the groups (Figure 1).     The study highlighted a few salient points: (1) although there was no difference in baseline hemodynamics, patients with BAV had larger aortic root dimensions; (2) over time, there was no difference in the progression of the aortic valve severity between the BAV and TAV groups; and (3) patients with BAV were not at an increased risk of aortic valve replacement (even though the trend suggested so), heart failure and mortality. Patients with BAV may have progression of aortic dilatation at a rate comparable to those with TAV, but they progressed from a larger dimension at baseline and at a younger age underscoring the importance of close surveillance in this particular group of patients. One of the flaws of this study lies in the fact that the aortic dimensions were performed using echocardiogram rather than CT or MRI scans, which were known to have a lower rate of measurement errors (ref).   Reference Kebed K, Sun D, Addetia K, Mor-Avi V, Markuzon N, Lang RM. Measurement errors in serial echocardiographic assessments of aortic valve stenosis severity. Int J Cardiovasc Imaging. 2020;36(3):471-479.   

Aortic distensibility in Marfan syndrome: a potential predictor of aortic events? van Andel MM, de Waard V, Timmermans J, Scholte AJHA, van den Berg MP, Zwinderman AH, Mulder BJM, Groenink M. Open Heart. 2021 Oct;8(2):e001775. doi: 10.1136/openhrt-2021-001775.PMID: 34702778 Free PMC article.   Take Home Points: Patients with Marfan Syndrome (MFS) have increased morbidity and mortality in relation to aortic dilatation – chiefly involving the aortic root - and aortic dissection Aortic distensibility at all levels is reduced at a young age in adults with MFS, and is inversely related to aortic dilatation rate Aortic distensibility measured by CMR is not a suitable predictor of aortic events. Commentary from Dr. Timothy Roberts (Melbourne, Australia), section editor of ACHD Journal Watch: Progressive aortic dilatation – especially of the aortic root – and subsequent aortic dissection is the leading cause of morbidity and mortality in patients with Marfan syndrome (MFS). Prophylactic aortic root surgery is performed to mitigate this risk based on threshold values for aortic diameters, with aggressive surgical intervention resulting in improved life expectancy over recent decades. The distal aorta is also at risk of dissection, often at near normal diameters, after aortic root surgery. The authors of the current study hypothesized that aortic distensibility could act as a potential predictor of distal aortic events, with the aim to evaluate aortic distensibility as a predictor of aortic complications in MFS patients over time. They also sought to assess differences in rates of decline of distensibility in men versus women, and to assess the influence of medication use or aortic surgery on the rate of distensibility in individuals with MFS.   A retrospective analysis of MFS patients who participated in two MRI based trials through Amsterdam UMC was performed. The first trial between 1996-2002 provided baseline characteristics of the study population, and the second between 2008-2012 offered additional information on medication use and events. Follow up data regarding aortic root replacement, aortic dissection and death was available until 2018 through an extended database. Only patients who completed both trials (comprising four MRI studies) were included in this analysis. All CMR scans were performed with a 1.5 Tesla MR system, using commercially available gadolinium-enhanced spoiled gradient echo techniques to visualize the entire aorta. High resolution gradient echo pulse sequences were applied perpendicular to the aorta in the ascending aorta (level 1), the descending thoracic aorta at the level of the bifurcation of the pulmonary artery (level 2), and the descending aorta at the level of the diaphragm (level 3). Blood pressure was measured non-invasively during each CMR scan. Aortic distensibility was re-measured and re-calculated per patient on all four scans at each level by a single analyst using a software. Distensibility at all levels was analyzed using linear mixed-effects regression models. Linear regression lines were found to best fit the distensibility data. Additional fixed effects were sex, medication use and aortic root surgery as time-dependent covariates, as both main-effects and their interactions with age. A change point model evaluated change in rate of distensibility loss before and after surgery and before and after start of medication use.   Of 78 adult patients participating in the first trial (1996-2002), 41 were also included in the second trial (2008-2012) and of these, 35 patients had complete CMR and blood pressure data available to be utilized in the current study. All had diagnoses of MFS according to the Ghent criteria of 1996. Sixteen (46%) of subjects were female (Table 1). At baseline, aortic dimension was significantly higher in men at all levels as compared to women. None of the 35 patients had undergone aortic root surgery, whereas at follow up in 2018 (22 years), 19 patients (54%) had undergone prophylactic aortic root surgery and three of these experienced a Type B aortic dissection at some point after their surgical intervention.     Aortic distensibility at all levels decreased approximately linearly with age and was significant at level 2 and level 3 before and after correction for blood pressure (Figure 3).     At baseline, distensibility at all levels was higher in women, and deteriorated over time. Men had low distensibility at inclusion, without further decline over time. Compared to unmatched healthy control data described in available literature, men with MFS in this cohort had a similar rate of decline in distensibility at level 2, whereas women with MFS had a greater rate of decline at this level than in controls. Men with MFS underwent aortic root surgery at a significantly younger age than women in this cohort (37 vs 44 years, p<0.001), noting significantly greater aortic root dimensions at the time of inclusion in men versus women (45 vs 40 mm, p<0.001).   Rate of distensibility loss did not differ during follow up in patients with native aortic roots and those who had undergone prophylactic aortic root surgery. Similarly, no difference was observed in the setting of either beta blocker or losartan prescription.   The authors conclude that patients with MFS have low distensibility at all levels of the aorta from a young age, but that aortic distensibility is not a suitable predictor of aortic events. The study has several inherent limitations, namely the retrospective nature, small sample size, and reliance on data of unmatched healthy controls described in literature. Correction for blood pressure was also reliant on single-point measurements during CMR testing. Ultimately, accurate prediction of aortic events after aortic root surgery remains elusive.