Adult Congenital Heart Disease

Prevalence of pulmonary hypertension in adults after atrial switch and role of ventricular filling pressures. Miranda WR, Jain CC, Connolly HM, DuBrock HM, Cetta F, Egbe AC, Hagler DJ. Heart. 2020 Oct 7:heartjnl-2020-317111. doi: 10.1136/heartjnl-2020-317111. Online ahead of print. PMID: 33028672   Take Home Points: In patients palliated with an atrial switch repair for transposition of the great arteries (TGA): Prevalence of an elevated systolic RV end-diastolic pressure was low (1/3 of patients) Almost 60% had an increased pulmonary arterial wedge pressure (PAWP), with prominent V waves Elevation in pulmonary pressures was present in nearly all patients who had a concomitant elevation in PAWP Commentary from Dr. Blanche Cupido (Cape Town, South Africa), section editor of ACHD Journal Watch: Both systemic RV systolic and diastolic dysfunction are well known complications after atrial switch procedures for Transposition of the Great Arteries (TGA). The contribution and effect of atrial baffles on cardiac output and ventricular filling is poorly understood. This is a retrospective review aimed at assessing the prevalence of elevated systemic filling pressures and pulmonary arterial hypertension late after atrial switch repairs. All adult patients with TGA and an atrial patients who underwent cardiac catheterization at the Mayo Clinic between January 2004 and December 2018. Patients with single ventricle physiology and those with atrial switch take-downs were excluded. Forty-two patients were included in the analysis. Their mean age at time of cardiac catheterization was 37.6 years, the median age at atrial switch surgery was 15 months. 90.5% of patients had a Mustard palliation. In 36 patients (85.7%), moderate or greater RV systolic dysfunction was noted. The mean sRVEF was 33%. In 35.7%, moderate or greater TR was noted. In terms of cardiac Catheterisation data: Pulmonary venous baffle obstruction in 16.7% Systemic venous baffle obstruction in 54.7% (in 10 cases percutaneous interventions were performed) Mean sRVEDP 13.2mmHg ±5.1mmHg. Mean Right PAWP 18.9, mean Left PAWP 18.5mmHg. sRVEDP was significantly lower than both right and left PAWP, even once baffle obstruction was excluded (right difference -2.4mmHg, left difference -2.5mmHg, p=0.02 and 0.004 respectively). Pulmonary venous baffle stiffness therefore likely plays a significant role in ventricular filling pressures. An elevated sRVEDP >15mmHg was seen in 35.1% of patients (older at the time of atrial switch with no other clinical differences). An elevated PAWP >15mmHg seen in 58.1% of patients (more likely to have a higher prevalence of NYHA class 3, to be on diuretic therapy, to have moderate or greater RV systolic dysfunction, and a lower EF. Pulmonary hypertension was seen in 47.5% of patients (n=17). Median PVR 1.3 Woods units. Among those with pulmonary hypertension, PAWP > 15mmHg in all but one patient. In addition to the systolic and diastolic dysfunction in the systemic RV, the pulmonary venous baffle has an important role in augmenting preload and on ventricular filling pressures as shown in this study by the relatively normal/low RVEDP and the elevated PAWP- with no end-diastolic gradient and a large v wave (as shown above). This is attributed to a combination the pulmonary venous atrium being of a small size compared to the left atrium, the baffle is non-distensible/partially calcified and increased atrial fibrosis/scarring.

Aorta size mismatch predicts decreased exercise capacity in patients with successfully repaired coarctation of the aorta. Mandell JG, Loke YH, Mass PN, Opfermann J, Cleveland V, Aslan S, Hibino N, Krieger A, Olivieri LJ. J Thorac Cardiovasc Surg. 2020 Oct 7:S0022-5223(20)32707-0. doi: 10.1016/j.jtcvs.2020.09.103. Online ahead of print. PMID: 33131888   Take Home Points: In patients with repaired coarctation of the aorta: Ascending to descending aorta size mismatch is associated with a decrease in exercise tolerance. Patients with ascending : descending aortic diameter of close to 1 had the best exercise capacity. The geometry of the aortic arch and the normalized aortic dimension were not associated with exercise capacity. Commentary from Dr. M.C. Leong (Kuala Lumpur, Indonesia), section editor of ACHD Journal Watch: Despite a successful initial repair, patients with coarctation of the aorta (CoA) remain to be at risk of long term morbidities. One of such is the decreased in exercise capacity. A decreased in exercise capacity does not only affects the quality of lives of patients, but it also increases the risk of hospitalization and death. In this paper, the authors sought to evaluate the relationship between aortic arch geometry, size and flow characteristics, and exercise capacity in patients with repaired CoA. The authors studied the above mentioned in an interesting way. Firstly, they looked at the patients with repaired CoA, who had a cardiac magnetic resonance (CMR) and cardiopulmonary stress test and achieved anaerobic threshold, within their database. Correlations were sought between the aortic arch geometry (Romanesque which is normal and Crenel and Gothic which are abnormal – Figure 1), the dimensions of the aorta measured at the usual locations, and the ascending and descending aortic flow measured on phase contrast imaging. Subsequently, the authors, innovatively, created a mock circulatory system to mimic circulatory flow within the arch by printing the 3D model of repaired CoA of all the subjects and measured the flow and pressures within the 3D arch models at rest and exercise, to simulate the effect of the flow of blood within the repaired arches during these conditions – Figure 2.   15 patients (mean age 26.8 8.6 years), of which 6 had bicuspid aortic valve, were recruited. Baseline characteristics were as tabulated in Table 1 and 2. The authors found that exercise capacity had a significantly positive correlation with normalized descending aortic diameter (DAo) diameter. Patients with a smaller ascending aorta: descending aorta diameter ratio (DAAo/DDAo) had better exercise capacity – Table 3 & Figure 3. Patients with DAAo/DDAo close to 1 had the best exercise capacity while worse peak oxygen consumption (VO2) was associated with a smaller DAo and a larger AAo. Normalised aortic root, sinotubular junction, AAo and isthmus diameters did not correlate with exercise capacity. Similarly, the geometry of the arch did not correlate to the VO2. In the mock circulatory simulation study, the percentage of DAo flow at rest and during exercise correlated negatively to DAAo/DDAo (rho = -0.68, p<0.01; and rho = -0.59, p=-0.02) and the ratio of percent of DAo flow in exercise to rest was positively correlated with DAAo/DDAo (rho=0.64, p<0.01) and negatively correlated with VO2 (rho =-0.60, p=0.02) – Figure 6. This study demonstrated that the ascending : descending aortic size mismatch is an important cause of exercise intolerance. Our initial perception that a smaller size aortic arch or an abnormal geometry of the aortic arch might cause an increased in flow resistance and a long term implication to the left ventricular muscles was not translated into a decrease in exercise capacity, nor is a dilated aortic root which may potentiate energy loss as blood flows through a large AAo. Rather, a smaller DAo is more closely related to exercise capacity rather than the dilated AAo which may be due to limited perfusion to the lower limbs.

Association of Damaging Variants in Genes With Increased Cancer Risk Among Patients With Congenital Heart Disease. Morton SU, Shimamura A, Newburger PE, Opotowsky AR, Quiat D, Pereira AC, Jin SC, Gurvitz M, Brueckner M, Chung WK, Shen Y, Bernstein D, Gelb BD, Giardini A, Goldmuntz E, Kim RW, Lifton RP, Porter GA Jr, Srivastava D, Tristani-Firouzi M, Newburger JW, Seidman JG, Seidman CE. JAMA Cardiol. 2020 Oct 21:e204947. doi: 10.1001/jamacardio.2020.4947. Online ahead of print. PMID: 33084842   Take Home Points: There is a significant genetic component to the known increased rates of cancer in patients with congenital heart disease compared to the background population. There is no association between a particular cancer risk gene and specific congenital heart disease sub-type. Commentary from Dr. Helen Parry (Leeds UK), section editor of ACHD Journal Watch: Objective of the study: To analyse the frequency of rare loss of function (LoF) cancer risk genes in a large cohort of patients with congenital heart disease Method: Genetic analysis was performed on participants in the Paediatric Cardiovascular Genetics consortium (n=4443) and controls (n=9808). Their genetic data were analysed for 723 genes associated with cancer risk, 38 of these were previously associated with congenital heart disease and 227 were LoF variants. These genes were previously identified and held on the Catalogue of Mutations in Cancer- Cancer-Gene consensus database. Frequency of the above genetic variants were analysed in the cohort with congenital heart disease and compared with the control cohort. Binomial testing was performed and significance was taken as p value < 0.05. A separate sub-analysis was performed for 7 genes with multiple LoF variants associated with extra cardiac anomalies in patients with congenital heart disease. Results: The table shows analysis of the frequency of the above genetic variants in the congenital heart disease cohort versus controls. Genes analysed Number of gene variants Odds ratio 95% CI P value Cancer risk genes 723 1.34 (1.21-1.49) 2.31 × 10−11b Cancer risk genes also associated with CHD 38 7.19 (4.23-12.22) <2.2 × 10−16b LoF mechanisms 227 1.43 (1.21-1.69) 1.58 × 10−7 There was no association between a particular cancer risk gene and specific congenital heart disease sub-type. The prevalence of seven cancer risk genes with multiple LoF variants associated with extra cardiac anomalies in patients with congenital heart disease was also tabulated (not replicated here as sub-analysis with very small numbers). Conclusions: There is a significant genetic component to the known increased rates of cancer in patients with congenital heart disease compared to the background population. Critique Positive aspects: Large cohort available for genetic analysis. Genes identified and validated by a well-recognised and independent database were used to form the basis of the study. Comprehensive cover of the genes of interest. Provides some insight into an topic with relatively little research. Negative aspects: There was almost no reference to potential confounding factors: were any of the gene variants also more common in individuals with particular behaviours also associated with cancer, e.g. smoking or substance misuse? The study was limited to patients of European extraction. There were no real details regarding the potential clinical relevance. There was a comment at the end of the paper that this may help guide screening programmes in the future but without any expansion on whether this will be limited to specific cancers or how this might work in a practical sense. The analysis looking at multiple LoF variants associated with extra cardiac anomalies in patients with congenital heart disease had such small numbers it would be very difficult to draw any conclusions, this has been largely omitted from this review as a result.