Adult Congenital Heart Disease

Predictors of left ventricular reverse remodelling after coarctation of aorta intervention. Egbe AC, Miranda WR, Connolly HM.Eur Heart J Cardiovasc Imaging. 2021 Sep 20;22(10):1168-1173. doi: 10.1093/ehjci/jeaa199.PMID: 33020809   Take Home Points: The authors assessed a number of measures of severity of coarctation of the aorta to the effects of prolonged left ventricular pressure overload, in addition to the effect of residual coarctation, finding aortic isthmus ratio had the strongest relationship to left ventricular mass and residual ratio had the strongest correlation with LV reverse remodelling post intervention.   Commentary by Dr. Simon MacDonald (London, UK), section editor of ACHD Journal Watch: Several measures can be used to determine coarctation of the aorta (CoA) severity. It is unclear what are the most reliable in determining left ventricle (LV) changes over time and, post intervention, what may predict LV remodelling. LV hypertrophy and both systolic and diastolic dysfunction are predictors of cardiovascular mortality.   In this single centre study from the Mayo Clinic they examined adult patients with CoA diagnosis from the Mayo Adult Congenital Heart Disease (MACHD) Registry, containing all adult congenital heart disease patient data from the Mayo Clinic from Jan 1985- 31 December 2018. Patients with significant aortic valve disease, significant mitral valve disease and patients with aberrant origin right subclavian arteries, as possible confounders, were excluded. They looked at LV remodelling using echo parameters of LV mass index (LVMI), LV global longitudinal strain (LVGLS), tissue Doppler early velocity (e’) and ratio of mitral inflow early velocity and tissue Doppler early velocity (E/e’) as measures of LV dysfunction at first clinical evaluation within the study period. They looked at indices at baseline and 5 year post intervention.   They used Doppler mean (peak) gradient, systolic blood pressure (SBP), upper-to-lower extremity systolic blood pressure (ULE-SBP) gradient and aortic isthmus ratio as markers of CoA severity. They looked at data obtained 12 months post intervention. CT and MRI were reviewed with aortic isthmus ratio defined as the smallest CoA diameter divided by the diameter of the descending aorta at the level of the diaphragm. Multivariate regression analysis was used to assess the correlation between CoA severity and LV remodelling indices, adjusting for age, sex, LVEF, hypertension history and use of medication, and age at time of repair. Receiver operating characteristic curves were used to determine the threshold of residual CoA that predicted adverse remodelling.   546 patients met inclusion criteria, 144 (26%) and 402 (74%) with native and recurrent CoA respectively. Of the 402 with prior repair 365 had surgical repair vs 33 with stent therapy, 4 with angioplasty alone. Median age of initial repair was 7 (0.9-17 years), with 288 (72%) having repair prior to 18yrs of age. 172 of the 546 patients (32%) underwent intervention with 165 (96%) having echo and imaging within 12 months of the intervention. 100 of these 165 (61%) had follow-up beyond 5 years without re-interventions.   The table below (their table 3) gives their main results, namely that there was a correlation between aortic isthmus ratio and LV remodelling indices. A residual aortic isthmus ratio <0.7 was the optimal cut-off to predict suboptimal LV reverse remodelling post intervention for LVMI. Residual Doppler peak gradient >29mmHg also predicted worse LV reverse remodelling.   Limitations: This was a single centre, retrospective study. No mortality or morbidity data was tied to the LV remodelling seen to confirm the potential benefits. It was unclear about what corrections were made for multiple testing. Assessing the potential benefits of surgery vs stenting and the optimal age for this was not done and most patients (128/172 or 75%) underwent surgical correction, stenting being perhaps though the most intervention in adult patients. They have a large patient cohort however and a lot of data points pre and post intervention. This would be their 12th paper on this cohort since 2020, some with overlapping themes. Their papers (DOI: 10.1016/j.jacc.2019.12.047 in 2019 and doi:10.1161/CIRCHEARTFAILURE.119.006651 in 2020) also report the strong correlation of aortic isthmus ration on LV pararameters. Overall this helps provide guidance on what measures are useful in assessing CoA severity and their effects on LV remodelling. Aortic isthmus ratio may be the most useful correlate of LV remodelling and residual post aortic isthmus ratio post intervention may predict LV remodelling afterwards.     

Non-invasive biomarkers of Fontan-associated liver disease. Emamaullee J, Khan S, Weaver C, Goldbeck C, Yanni G, Kohli R, Genyk Y, Zhou S, Shillingford N, Sullivan PM, Takao C, Detterich J, Kantor PF, Cleveland JD, Herrington C, Ram Kumar S, Starnes V, Badran S, Patel ND. JHEP Rep. 2021 Sep 14;3(6):100362. doi: 10.1016/j.jhepr.2021.100362. eCollection 2021 Dec.PMID: 34693238   Take Home Points: FALD begins earlier than first thought following Fontan completion Platelet count, AST: platelet ratio, bilirubin and FIB-4 scores all correlate with the degree of fibrosis Progression of FALD to bridging fibrosis or cirrhosis appears to be associated with increased mortality Commentary by Dr. Helen Parry (Leeds, UK), section editor of ACHD Journal Watch: Background: Patients with a Fontan circulation are known to have a significantly increased likelihood of hepatic fibrosis, cirrhosis and hepatocellular carcinoma; a pattern referred to as Fontan associated liver disease (FALD). Multiple factors may contribute to the pathophysiology including chronically raised central venous pressure, hypoxia and low cardiac output.   Objectives: To assess the association between disease seen on biopsy and non-invasive biomarkers of FALD To assess the prevalence and associations of FALD in the Hispanic population Methods: This was a single center study in Los Angeles. The patients were studied retrospectively and identified by local database. Cardiac catheter studies are routinely performed roughly 10 years following completion of the Fontan connection in this center and transjugular hepatic biopsies are performed at the same time. Blood test results for ALT, AST, ALP, bilirubin, GGT, blood urea nitrogen, creatinine, albumin, glomerular filtration rate, prothrombin time, full blood count and BNP taken within 6 months of the biopsy. The pathologists who examined the biopsies were blinded to the patient’s clinical details and scored them according to the Congestive Hepatic Fibrosis Score (CHFS) where scores 0-2b were classed as less severe FALD and 3-4 more severe. This separates fibrosis alone (1-2b) from bridging fibrosis (3) and cirrhosis (4).   Results: A total of 106 patients were included in the study: 69% were Hispanic, the mean age was 14.4 years +/- 3.5 years and 27% met criteria for obesity. The biopsy was taken an average of 10-11 years post Fontan completion. One patient experienced bleeding at the time of the biopsy and this was treated with gel foam embolization. The most common underlying pathologies were hypoplastic left heart syndrome (39%) and tricuspid atresia (17%). One hundred and five of the 106 patients had some degree of hepatic fibrosis; 35 % had bridging fibrosis and 5.7% cirrhosis. Bridging fibrosis was associated with lower platelet count, increased AST: platelet ratio, raised bilirubin and raised FIB-4 score. Temporal change in platelet count was associated with the degree of fibrosis. Median follow up post biopsy was 2 years. The Kaplan Meier analysis showed CHFS was associated with reduced survival (p=0.027). Seven patients died during follow up; 2 had CHFS 0-2b and the remaining 5 had CHFS of 3-4. Causes of death included complications relating to placement of epicardial pacing systems, progressive heart failure, sepsis and pulmonary hemorrhage.   Strengths Provided data for Hispanic patients, perhaps underrepresented in other studies Provided histological images used to demonstrate the degree of fibrosis Findings were consistent with existing literature A range of non-invasive biomarkers were investigated in order to draw the most useful predictors Weaknesses/ suggestions for improvement The statistical significance of association between more advanced FALD and death is questionable as there were are very small number of mortalities The follow up period post biopsy was short (2 years median) No comparison was made between biopsy results and non-invasive modalities such as ultrasound or MRI No comparison was made between cardiac factors such as ventricular impairment or atrio-ventricular valve function, and the development of FALD A multi-centre study may have enhanced likelihood of identifying any racial differences in Hispanic versus Caucasian patients: do we need to be even more vigilant in either of these groups?