Adult Congenital Heart Disease

Huntley GD, Danford DA, Menachem J, Kutty S, Cedars AM. Donor Characteristics and Recipient Outcomes After Heart Transplantation in Adult Congenital Heart Disease. J Am Heart Assoc. 2021 Jul 20;10(14):e020248. doi: 10.1161/JAHA.120.020248. Epub 2021 Jul 9. PMID: 34238025; PMCID: PMC8483491.   Take Home Points: Volume and proportion of patients with adult congenital heart disease (ACHD) requiring heart transplantation (HTx) is rising rapidly, while donor availability remains low Registry data has shown longer wait times for HTx in ACHD patients compared to those without ACHD (non-ACHD), a lower probability of high-priority listing status, and a lower likelihood of transplantation This current large retrospective analysis of data from Scientific Registry of Transplant Recipients in the USA between 2000 – 2016 has identified very few differences in donor characteristics between HTx recipients with ACHD and non-ACHD, but longer waitlist times for Status 1A-listed ACHD patients Post-transplant outcomes demonstrated worse early mortality (days 0 - 30) in ACHD HTx recipients, similar intermediate mortality (31 days – 4 years) and superior late mortality (> 4 years); no donor characteristics were found to be associated with mortality Unique donor selection criteria in ACHD are not indicated based on the findings from this retrospective analysis. Commentary from Dr. Timothy Roberts (Melbourne, Australia), section editor of ACHD Journal Watch: There is a persistent shortage of cardiac allografts for ACHD and NCHD patients awaiting HTx, resulting in considerable time spent on waitlists and high waitlist mortality. Despite this, a low donor heart acceptance rate has been observed across all patients which may suggest an increasing avoidance of risk. The refusal of a donor heart may be due to various reasons, although evidence to support refusal is limited to only a few factors including increasing age, ischaemia time, history of stroke, diabetes mellitus, coronary artery disease, substance abuse, and in some cases age, sex and weight mismatch.   The current study group hypothesized that greater donor selectivity does not improve post-HTx outcomes for patients with ACHD awaiting HTx, but rather may lengthen waitlist times and worsen post-HTx outcomes.   The Scientific Registry of Transplant Recipients (USA) was utilized to perform a retrospective analysis of adult patients listed for HTx between 2000 and 2016. Patients were separated according to their underlying disease being ACHD or NCHD and further subcategorized into candidates (pre-HTx) and recipients (post-HTx). The primary outcome was waitlist time for candidates and posttransplant survival for recipients. All candidate variables were considered, as were all donor and recipient variables provided in the SRTR Database.   A total of 1649 patients with ACHD were listed for HTx during the study period, of which 903 underwent HTx; for NCHD patients 35274 of 54330 listed patients proceeded to HTx. Key significant differences between ACHD and NCHD HTx candidates were:   Smaller proportion of ACHD patients initially listed as Status 1A (45% vs. 52%; p<0.001) Longer time on waitlist for ACHD patients (253 +/- 391 vs. 199 +/- 316 days; p<0.001) Key significant differences in donor characteristics to ACHD vs. NCHD HTx recipients were younger age, shorter height, lower weight, more female sex, lower INR, and higher LV ejection fraction (see Table 2, below).     Survival curves demonstrated worse 30-day mortality for ACHD HTx recipients, similar survival rates to 4 years, and superior survival beyond 4 years (Figure 1, below). Multivariable models were constructed to identify donor characteristics associated with post-HTx mortality in each risk period including HTx recipients with ACHD or NCHD, followed by models of post-HTx mortality for only ACHD HTx recipients in each risk period. No donor characteristics were associated with early or intermediate mortality in ACHD. Donor prerecovery steroid use and meeting high-risk donor criteria according to the Centers for Disease Control and Prevention were associated with late mortality (HR 2.891 [95% CI 1.189-7.029, p=0.006]; and HR 2.612, [95% CI 1.327-5.142, p=0.006], respectively). Donor history of other drug use was associated with late survival (HR 0.46, 95% CI 0.248-0.850, p=0.013).   Analysis was also limited to patients with a final listing status of 1A given patients with ACHD listed as 1A experience longer waitlist times and worse waitlist outcomes. Candidate, recipient and donor characteristics were largely similar to the total cohort. Survival curves suggested a similar 3-period, time-dependent difference in mortality risk. Multivariable models did not identify any difference in donor-specific risk factors that were significantly associated with early, intermediate or late mortality.   Donor characteristics associated with waitlist time in ACHD patients listed as status 1A identified Epstein-Barr virus nuclear antigen negative donor, a donor without an alcohol use disorder, and a cytomegalovirus (CMV) negative donor as being associated with longer waitlist times. Interestingly, none of these three variables were significantly associated with mortality irrespective of listing status.   The authors conclude that the absence of donor characteristics associated with early or intermediate mortality, and minimal factors associated with late mortality, provide support against the need to create unique donor selection criteria in ACHD HTx candidates. The high early perioperative mortality in ACHD HTx recipients but superior long term survival mirrors that of other registry data, the latter thought to be due to lower comorbidity burden.   It should be noted that the retrospective nature of this study, missing data points and absence of congenital anatomy or prior congenital operations limit the statistical accuracy and strength of the data provided, although certainly shines a light on the potential for HTx teams to liberalise donor criteria.   

20: Stassen J, De Meester P, Troost E, Roggen L, Moons P, Gewillig M, Van De Bruaene A, Budts W. Covered stent placement for treatment of coarctation of the aorta: immediate and long-term results. Acta Cardiol. 2021 Jul;76(5):464-472. doi: 10.1080/00015385.2020.1838126. Epub 2020 Oct 28. PMID: 33108973   Watch Commentary by Dr. Helen Parry (Leeds, UK), section editor of ACHD Journal: Introduction: Coarctation of the aorta accounts for 5-8% of congenital heart disease. Ten per cent of infants who undergo surgical intervention need further intervention in adulthood. Balloon only angioplasty was a popular choice for these patients, but there was a high rate of recurrence. Aortic wall injury and obstruction of the aorta were also noted complications. Bare metal stents were also used in this context but were associated with aneurysm, rupture, dissection and death. The use of covered stents in treatment of coarctation of the aorta has become more widely spread. The study provides a contribution to the literature regarding their safety and efficacy.   Methods: This was a single centre, retrospective, observational study. Adult patients were included if they had an invasive gradient across the coarctation of >= 20 mmHg, or if the luminal diameter at the coarctation was 50% or less of the vessel. Children included in the study according to their diagnosis of hypertension, in this study, classed as >95th centile in age and gender matched controls.   As this was a retrospective study, there was variability in the follow up involved. Most patients were seen around 3 months post procedure and variably thereafter. Data for the mean systolic blood pressure gradient between the right upper limb and left lower limb were extracted and analysed where available. Clinical records were assessed for post procedure antihypertensive medications and for complications relating to the insertion of the covered stent. Results: The numbers of patients included and followed up are shown in the figure below, which is a copy of the flow chart included in the paper:   The mean age of the patients involved was 23.9 years +/- 15.8. A total of 102 stents were deployed in 89 patients. Peri-procedural complications were those occurring within the first 3 months. The peri-procedural complication rate was 4.5% relating to vascular issues at the access site. Four patients had late complications: 2 patients developed stent fractures requiring further procedures and 2 patients developed new aneurysms following stent insertion. Patients with very tight narrowing who had planned staged treatment were not classed as requiring re-intervention.   The mean systolic blood pressure gradient comparing the right upper limb and left lower limbs was 38 mmHg +/-24 mmHg, at 3 months; this had fallen to 10 +/- 20 mmHg and was 10 +/- 17 mmHg at 12 months. At latest follow up, the blood pressure gradient for 56 patients was practically non-existent at -7+/- 18 mmHg. The mean follow up period was 6.6 years +/-3.7 years.   Data regarding blood pressure medications were also assessed. Thirty patients were taking anti-hypertensive medications post stent, 13 of these patients had reduced these medications at 1 year follow up. The 26 patients who were hypertensive (>140/90 mmHg) but not receiving medications were normotensive without medication at 1 year post covered stent insertion. However, at latest follow up, roughly 20% of all subjects were on antihypertensive medications.   Positive aspects of the study: Real-world data Adds to the data available and will aid the consent process in providing formal numbers of patients who developed complications. Describes the expected improvement in mean blood pressure between the right upper and left lower limbs to allow comparison during follow up by other teams assessing the relative success of their procedures Negative aspects: The retrospective nature if the study meant that patients were not followed up at regular intervals in a uniform way, making the post procedure imaging very variable and posing the question whether further complications actually occurred but were not discovered The single centre nature of the study makes it difficult to extrapolate findings for other units A significant number of patients were lost to follow up, making the data incomplete No patient characteristics were provided for the patients who developed late complications, which may have been helpful in identifying patients who were high risk

21: Karunanithi Z, Andersen MJ, Mellemkjær S, Alstrup M, Waziri F, Skibsted Clemmensen T, Elisabeth Hjortdal V, Hvitfeldt Poulsen S. Elevated Left and Right Atrial Pressures Long-Term After Atrial Septal Defect Correction: An Invasive Exercise Hemodynamic Study. J Am Heart Assoc. 2021 Jul 20;10(14):e020692. doi:10.1161/JAHA.120.020692. Epub 2021 Jul 14. PMID: 34259012; PMCID: PMC8483478.   Take Home Points: Patients with corrected ASD have elevated RA and LA pressures at rest and during exercise (either due to intrinsic atrial abnormality and/or alteration of the LV diastolic properties) These changes are present despite having a preserved exercise capacity. The abnormal atrial compliance and systolic atrial function noted here, may be a contribute to the long term atrial fibrillation risk Commentary from Dr. Blanche Cupido (Cape Town, South Africa), chief section editor of ACHD Journal Watch: Patients with ASD, despite correction, have a higher mortality and morbidity rate compared to the general population. Surgical and percutaneous correction aims to reduce RV volumes, RA and LA volumes and RV function. This is a single center study from Denmark assessing the physical activity, cardiac performance and invasive exercise hemodynamics in patients with a corrected ASD – the hypothesis is that despite correction, the hemodynamic effects are lasting and may explain some of the long term complications if ASD like arrythmias and propensity to pulmonary infections.   Patients with an isolated secundum ASD between August 2018 and October 2019 were enrolled. The diagnosis had to have been made by 2 years of age and should be at least 3 years out since their intervention. A total of 38 patients were enrolled (19 surgical correction, 19 percutaneous closure). Nineteen healthy age-matched controls were enrolled. All patients had a right heart catheterization at rest and during exercise with simultaneous expired gas recordings and an echocardiogram. A semi-supine ergometer was used workload increased at 3-minute intervals.   Table 1 shows that the 2 cohorts were similar in terms of demographic criteria. Echocardiography at rest showed no differences in the LV and RV volumes between the 2 groups. Furthermore, the LV systolic function was preserved and similar in both groups. The E/A ration in the ASD group trended higher but this was not statistically significant. Both TAPSE and RV longitudinal strain was reduced in the ASD compared to the control group though still within the limits of normal.     Resting heart rate was higher in the ASD. Group. Peak oxygen uptake was also similar between the 2 groups (35.2±7.5 ml/kg/min in controls and 32.7±7.7 ml/kg/min in ASD group, p=0.3). Table 3 shows the hemodynamic findings between the 2 groups. At rest, there were no differences between the control group and those with an ASD in terms of mean right atrial pressure (RAP), mean pulmonary wedge pressure or mean pulmonary artery pressure. With exercise, the ASD group had a significant increase in pulmonary pressures, pulmonary wedge pressures and trans-mural filling pressures (the latter 2 parameters perhaps implying abnormal exercise induced LV diastolic properties). Neither time since intervention nor the type of intervention correlated significantly with these findings.     Pulmonary wedge v wave was increased at rest and on exercise in the ASD group implying impaired LA compliance. In the right atrium, the RA a wave increased significantly in the ASD group compared to controls. (Figure 1)   An abnormal exercise response was defined as a mean pulmonary wedge pressure ≥25mmHg and/or mean pulmonary artery pressure ≥35mmHg at peak exercise. All participants in the control group had a normal exercise response. A third of the ASD group had an abnormal exercise response (n=13). These patients demonstrated significantly elevated mean pulmonary wedge pressures and peak a and v wave pressures compared to both the control group and those ASD patients with a normal exercise response. Since LVEDP was not measured directly, one can’t be certain if this represents intrinsic LA abnormalities or impaired LV diastology or a combination of the 2 (Figure 2).   Furthermore, transmural filling pressures are increased at both rest and on peak exercise in this group most likely representing impaired LV compliance.