Adult Congenital Heart Disease

Partial Anomalous Pulmonary Venous Connection: Forty-Six Years of Follow-Up. Nielsen AKM, Hjortdal VE. World J Pediatr Congenit Heart Surg. 2021 Jan;12(1):70-75. doi: 10.1177/2150135120960482. PMID: 33407025   Take Home Points: In PAPVC, early surgical mortality is low. Late onset of brady- and tachyarrhythmias are common with half of these patients requiring permanent pacing. Event-free survival at 12 years of follow-up was 81%   Commentary from Dr. Blanche Cupido (Cape Town, South Africa), chief section editor of ACHD Journal Watch: Partial anomalous pulmonary venous connections (PAPVC) is a rare congenital anomaly most frequently involving the right upper pulmonary vein. Surgical correction results in suture lines which are substrates for arrythmias. The sinus node is also located close to the usual suture lines. Surgical techniques have over the last few decades evolved to try and minimize the arrhythmic complications. Long term outcome data pertaining to PAPVC correction is limited. In this retrospective Danish cohort study, the long-term outcomes after various surgical technique corrections of PAPVC are assessed in terms of sinus node dysfunction, arrythmias, PV stenosis, SVC graft dysfunction and mortality.   Patients operated for PAPVC between 1970 and 2010 were identified from the Danish surgical databases. After excluding those with scimitar syndrome and concomitant VSD, CTEPH and atrial isomerism, 83 patients were included in the study. Follow up was from date of surgery to May 2018 –the median duration of follow-up was 14.3 years (3-46 years). A late outcome event was defined as >30 days post-surgery.   The most frequently observed anomaly was of the right upper pulmonary vein, followed by scimitar syndrome then left pulmonary vein. Right sided veins were baffled through the RA via an ASD to the LA, the left sided vein anomalies were connected directly to the LA.   Of the 83 patients, 51% were women (n=42). The mean age of surgery was 25 ±24 years (wide range – 4 months to 77 years) with just over 50% being under the age of 18 at the time of surgery.   The distribution of surgical procedures is seen in table 1:     Single patch technique was performed in 36, two patch in 34, direct anastomosis in 10 and a conduit in 1. Every decade the number of surgeries increased with 60% of all surgeries done from 2000 to 2010. Five patients had right sided cryoablation as part of a study to prevent atrial arrythmias.   In the immediate post-operative period, 2 patients developed strokes (both over age 45). Eight patients (10%) died during follow-up at a mean age of 59 years. Only half of the deaths were cardiac in origin. Stenosis of the SVC (n=3) and pulmonary veins (n=2) was seen in a total of 5 patients (6%).   Only 47 patients had a pre-operative ECG – all had evidence of RBBB, RVH or right axis deviation. In 11 patients (13%), AF or atrial flutter was seen pre-operatively.   Late sinus node dysfunction was seen in 9 patients (11%) – 4 had bradycardia and 5 had sinus arrest ± AF/Aflutter. Pacemakers were implanted in 7 patients (8%) for sinus node dysfunction(n=5), cardiac resynchronisation therapy (n=1) and third degree AV block (n=1).   Early post-operative new onset AF/atrial flutter was seen in 8 patients (10%) – in 7 of them, this settled before discharge and they left hospital in sinus rhythm. The prevalence of late atrial fibrillation / flutter was 17%   In 81% (n=67), no arrythmias or need for pacing was noted. Figure 2 shows the even-free survival.     There was no statistically significant difference pertaining to the different surgical techniques and outcomes.   Conclusions: Late sinus node dysfunction and the need for permanent pacing are significant complications post surgery for PAPVC. At an average of 12 years post surgery, 11% had sinus node dysfunction and more than 50% needed pacing. There was no statistically significant difference between surgical technique and arrythmia outcomes. Late stenosis of PV or SVC was seen in 6%. Definitive conclusions are limited due to the retrospective nature and the surgical technique diversity in this study.   

Sacubitril/valsartan in the treatment of systemic right ventricular failure. Zandstra TE, Nederend M, Jongbloed MRM, Kiès P, Vliegen HW, Bouma BJ, Tops LF, Schalij MJ, Egorova AD. Heart. 2021 Jan 15:heartjnl-2020-318074. doi: 10.1136/heartjnl-2020-318074. Online ahead of print. PMID: 33452121 Free Article.   Take Home Points: There is a huge lack of evidential medical based treatments for patients with ACHD and heart failure. In patients with left ventricular systolic dysfunction, Sacubitril-Valsartan (Entresto). has been proven to significantly reduces mortality and morbidity and clearly superior to ACE-I treatment in such patients. This study reports on 20 patients with a systemic RV who were switched from their ACE-I/ARB treatment to sacubitril-valsartan (and also taking a beta blocker). All patients had systemic RV dysfunction (EF <35%) and were ‘symptomatic’ despite taking a beta blocker and ACE/ARB pre change. Two thirds of patients had an atrial switch and the remainder ccTGA.6 month follow up data was obtained in 18/20 patients. A change from an ACE-I/ARB to sacubitril-valsartan resulted in: A fall in NTproBNP level from 950 ng/L to 358 ng/L (p<0.001). Improvement in Echo measured FAC and GLSIncrease in 6MWT from 564m to 600m (p=0.01). Improvement in Quality of life measures.     Commentary by Dr. Damien Cullington (Liverpool, UK), section editor of ACHD Journal Watch:   After many years of a lack of new medical therapies in heart failure and more than enough failures, it is refreshing to see the ‘Next Gen’ of agents coming over the horizon. The future is very bright in heart failure and it’s invigorating for all heart failure enthusiasts out there. PARADIGM-HF reported its findings in 2014 - on reflection, it has taken a very long time from publication to a mass roll out even in spite of the striking ‘in your face’ therapeutic positive effects of sacubitril-valsartan (SV).   Zanstra et al. selected ACHD patients for treatment with SV if the systemic RV function was significantly impaired (RVEF <35%) and patients were ‘symptomatic’ despite treatment with maximal tolerated beta blocker and ACE-I/ARB for at least 3 months. RVEF was measured either by echo and/or MRI. Symptoms were subjectively evaluated in out-patient clinic. Before initiation of SV, as part of standard care, all patients had an echo, cardio-pulmonary exercise test using bike ergometry, 6MWT, blood tests and quality of life assessments. The treatment protocol is shown in Figure 1.   Patient characteristics Twenty patients were initially enrolled with systemic RV heart failure – evenly split between men/women. Mean age was 46 ± 11 yrs. Two patients were withdrawn. Two thirds of the final analysis group had an atrial switch (n=12) and the remainder had ccTGA anatomy (n=6).   Results Change in clinical/echo data captured at baseline then at 6 months is shown in Tables 1 & 2. The percentage change in NTproBNP level from baseline to 6 months is shown in Figure 2. Temporal change in indices in quality of life is shown in Table 3.           Whilst one cannot say this data completely seals the deal on SV use in patients with a systemic RV impairment, there is much optimism here and it is well worth sitting up to take note. The majority of the group had grade I/II systemic AV valve regurgitation so perhaps this cohort comprises a more favourably responsive group to SV compared to such patient with more severe degrees of regurgitation who perhaps destined to fail faster and be more refractive to medical treatment – however this study is not designed to investigate this.   A switch from an ACE-I or ARB (of which there is little evidence to support use) to SV resulted in a drop in NTproBNP (one of the strongest independent prognostic markers); marginally improved RV performance within a relatively short space of time; improved 6MWT distance AND improved QOL. This is very promising.   I am not sure there is much further to add aside from the usual mantra of it being desirable to validate these findings in a larger, randomised dataset –realistically, is this going to happen?   Conclusions If heart failure with LV dysfunction is the fast line at the moment, ACHD heart failure is still very much confined to the slow lane (or even perhaps the hard shoulder). This was a very welcome article to read - yes, it isn’t a randomised controlled clinical trial but it’s very positive signposting.   One further question to ask is, when should one start treatment with SV? It seems somewhat counter-intuitive to patiently wait until the systemic RV has adversely remodelled, then failing with evolving symptoms before starting a restorative treatment. Surely we should be really thinking of starting treatment sooner rather than later before too much ground is lost. Prevention being better than cure. This requires further study.   Given that there is little evidence for the use of any other neuro-hormonal blocking agents in this niche group of patients, I’m fully behind the groups’ thinking and it certainly reflects /supports my current clinical practice – what about yours?   

Dynamic exercise changes in venous pressure and liver stiffness in Fontan patients: effects of Treprostinil. Possner M, Chaudhry A, Dillman JR, Urbina EM, Gao Z, McCoy C, Faust M, Rossiter HB, Powell AW, Mays W, Veldtman G. Cardiol Young. 2021 Jan 28:1-7. doi: 10.1017/S1047951121000159. Online ahead of print. PMID: 33504408   Take Home Points: A marked dissociation between peripheral venous pressure augmentation (average rise ~ 88%) and liver stiffness rise (up to 30%) during incremental exercise was observed; this suggests intrinsic compensatory mechanisms shelter the liver from acute haemodynamic shifts in Fontan patients. Treprostinil, an inhaled prostacyclin analogue, failed to attenuate venous pressure and liver stiffness responses to exercise.     Commentary by Dr. Timothy Roberts (Melbourne, Australia), section editor of ACHD Journal Watch: The Fontan circulation results in chronic venous pressure overload which is thought to contribute to Fontan-associated liver disease. During exercise, systemic venous pressure rises markedly without a similar augmentation of cardiac output. Inhaled pulmonary vasodilators have garnered interest as a therapy to improve Fontan haemodynamics by lowering systemic venous pressure and improving systemic ventricular pre-load and thus cardiac output. The aims of this study were:   To assess liver stiffness at rest and immediately following maximal exercise. To measure the acute venous pressure responses to maximal incremental and constant work rate exercise; and To assess the effects of an inhaled prostacyclin analogue, Treprostinil, on systemic venous pressure responses, exercise endurance, and aerobic capacity as well as ultrasound-derived liver stiffness pre- and post-exercise. This was a substudy to a larger prospective, randomised, double-blind, placebo-controlled cross-over trial examining the effects of inhaled Treprostinil on exercise endurance in young adults with a non-failing Fontan circulation. Inclusion criteria were age 18 years or older, and history of a Fontan palliation. Exclusion criteria were clinically unstable patients, Fontan pathway or intracardiac obstruction, ventricular dysfunction (EF < 40 %), uncontrolled arrhythmias, inability to perform exercise testing, obesity (BMI > 35), pregnancy or breast-feeding, and ongoing pulmonary vasodilator treatment. The primary outcome was change in liver stiffness measured using ultrasound sheer wave elastography following maximal exercise. Secondary outcomes included change in venous pressure at peak exercise, and changes in venous pressure, liver stiffness and exercise parameters in response to inhaled Treprostinil during and following incremental maximal exercise.   Figure 1 (below) illustrates the study protocol:   Fifteen patients were recruited, of which 14 completed the study and were included in the final results. Mean age was 27.7 +/- 8.1, 64% were female, and BMI 24 +/- 3.4. Underlying anatomy included tricuspid atresia (n=4), double inlet left ventricle (2), pulmonary atresia (2), and hypoplastic left heart syndrome (6). Most Fontan palliation types were lateral tunnel (n=9), with 2 atrio-pulmonary and 3 extra-cardiac Fontan type.   Liver sheer wave speed increased in 11 of 14 patients immediately after exercise (figure 2). The relative increase in sheer wave speed was 29 +/- 40 % on placebo and 22 +/- 32 % on Treprostinil (p=0.54). No significant correlation was seen with liver sheer wave speed and systemic venous pressure at peak exercise.     Peripheral venous pressures increased acutely during incremental (12.1 +/- 2.4 vs 22.6 +/- 8.0 mmHg, p < 0.001) and constant work rate exercise (12.5 +/- 2.5 vs. 23.4 +/- 5.2 mmHg, p < 0.001) on placebo. Treprostinil did not reduced venous pressures at rest nor at peak exercise during the incremental work rate exercise test (figure 3). There was no significant difference in VO2peak with placebo or Treprostinil (24.6 +/- 9.04 vs. 23.4 +/- 6.67 ml/kg/min, p = 0.19). Exercise endurance was significantly lower after inhalation of Treprostinil compared with placebo (5.19 +/- 0.89 vs. 5.82 +/- 1.23 minute, p = 0.02).     The observed “uncoupling” of venous pressure and liver stiffness may be explained by alterations in splanchnic blood flow precipitated by exercise. The authors suggest that exercise may acutely moderate hepatic inflow through diminished portal venous and hepatic arterial inflow and that this may relatively constrain acute hepatic congestion. Liver compliance may also vary between patients, mediated by perisinusoidal fibrosis that limits and contains the ability of increased blood flow to augment liver stiffness.   Study limitations include the small sample size, selection bias for well-functioning Fontan patients, lack of liver cirrhosis assessment, and absence of direct measurement of pulmonary vascular resistance. While Treprostinil failed to alter venous pressure and liver stiffness responses, its haemodynamic effect in a “sicker” Fontan population remains unknown and may warrant further assessment.