Adult Congenital Heart Disease

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 Nov;107(21):1725-1730. doi: 10.1136/heartjnl-2020-318074. Epub 2021 Jan 15.PMID: 33452121   Study Summary and Take Home Points: Data regarding the effectiveness of drug therapy in patients with systemic right ventricles such as those with L-loop TGA and D-loop TGA s/p an atrial switch are scarce. In one relatively small randomized trial that included 88 patients with systemic RV’s, treatment with Valsartan was compared to placebo. The authors of that trial reported that symptomatic patients receiving placebo experienced deterioration of the RV ejection fraction, whereas in the valsartan group, the ejection fraction remained stable over 3years of follow-up. In patients with systemic left ventricles, the combination of sacubitril and valsartan was superior to enalapril in reducing the risk of death and hospitalization for systolic heart failure, and this treatment is currently indicated in all symptomatic patients with heart failure with an LV ejection fraction ≤35 This paper summarizes the results of a single center cohort study performed in the Netherlands and aimed to investigate the feasibility and effects of sacubitril/valsartan treatment in patients with systemic RV’s. The study included 18 patients with systemic RV’s (12 s/p atrial switch operation for D-loop TGA and 6 with unoperated L-loop TGA, mean age 46+11years, 50% females) and RVEF<35% who remained symptomatic despite maximal tolerated doses of beta blockers and ARB’s/ACEi’s. The starting dose of sacubitril/valsartan was determined based on the dose of the ARB/ACEi’s taken by the patients prior to initiation of therapy, and the goal was to uptitrate the dose to 97/103 two times/day after 2-4 weeks. The target dose of 97/103mg two times/day was reached in 12 (67%) patients. Four patients (22%) had a maximum tolerated dose of 49/51mg and two patients (11%) had a maximum tolerated dose of 24/26mg two times/day After 6 months of therapy, a statistically significant decrease of 45% in NT-pro BNP levels was noted (median 950–>358ng/L, p<0.001). The authors report on a statistically significant but “clinically irrelevant” increase in potassium levels, and no change in the cohort’s GFR. Blood pressure did not decrease significantly after treatment initiation. On echocardiographic evaluations performed also after 6 months of therapy, there was an improvement in the systemic RV function as accessed by the fractional area change and in RV global longitudinal strain values but not by the “eyeballing” assessments. the RV end diastolic diameter and severity of tricuspid regurgitation did not change significantly after 6 months of therapy. The 6min walking distance slightly increased from a mean of 564m to 600 m (p=0.011). The NYHA functional class, weight and maximal exercise capacity (peak VO2, RER and maximal heart rate) as assessed with exercise testing were unchanged. After 6 months of treatment QOL parameters that improved included cognitive function, sleep and vitality(p=0.015, p=0.007 and p=0.037, respectively). Other QOL parameters such as social functioning and daily activities did not change. Commentary from Dr. Yonatan Buber (Seattle, USA), section editor of ACHD Journal Watch: Editor’s comments The number of studies that examined the potential benefits of novel heart failure medications such as Sacubitril/valsartan, GLP-1 inhibitors and others in adults with complex congenital heart disease is extremely small. This current study is a small non-randomized cohort trial that consisted of 18 patients with failing systemic RV’s followed over 6 months. Distinctive features of this study include the inclusion of NT-pro BNP as a biomarker to assess the response to therapy, the meticulous follow up protocol and the inclusion of several objective and subjective parameters to assess the response to therapy. The finding that similar to the PARADIGM HF trial, there was a decrease in NT-pro BNP levels may prove a mechanism of action of Sacubitril/valsartan that is also relevant in systemic RV’s (LV GLS and MAPSE did not change in this cohort after 6 months), and the changes in some of the echo parameters but not others are also promising and raise the hypothetical option that in longer follow up other echo parameters will change as well. The improvement in the 6 minute walk test is also encouraging, and the same consideration for the need of longer follow up period exists for the lack of change in the CPET parameters. The absence of significant side effects and the lack of decrease in blood pressure are encouraging, although only two thirds of the cohort reached the maximal treatment doses.   This was a non randomized trial with no control arm, and the authors did not report the outcomes of similar patients who were maintained on Enalapril or other medications taken by the patients. Hard clinical outcomes such as heart failure hospitalizations and death were not reported.   

Cardiovascular Morbidity and Mortality in Adult Patients With Repaired Aortic Coarctation. Meijs TA, Minderhoud SCS, Muller SA, de Winter RJ, Mulder BJM, van Melle JP, Hoendermis ES, van Dijk APJ, Zuithoff NPA, Krings GJ, Doevendans PA, Witsenburg M, Roos-Hesselink JW, van den Bosch AE, Bouma BJ, Voskuil M.J Am Heart Assoc. 2021 Nov 16;10(22):e023199. doi: 10.1161/JAHA.121.023199. Epub 2021 Nov 10.PMID: 34755532   Take Home Points: Cardiovascular events are common in repaired Coarctation of aorta (21% in this cohort) Arrhythmias and Aortic complications were most frequent cardiovascular events Risk of cardiovascular events increased with age 0.8% at 20 years to ~ 8% at 70 years Older age at repair and elevated LV mass index are associated with increased risk of cardiovascular events All-cause mortality was 3.3 times higher than the matched Dutch general population         Commentary from Dr. Shailendra Upadhyay (Connecticut, USA), section editor of ACHD Journal Watch: Coarctation of aorta (CoA) is one of the common CHDs. Long term issues include cardiovascular complications in majority, yet the knowledge of exact burden of cardiovascular disease in adult CoA is limited. Enrolled patients (n=920) cohort consisted of five tertiary referral centers in Netherlands, participants of the CONCOR prospective registry between 2002 and 2018 were included. All patients with surgical or trans-catheter CoA repair were included but univentricular circulation and transposition of the great arteries.   Cardiovascular events included: CAD, stroke or TIA, thoracic aortic complications (aneurysm or dissection), arrhythmia, heart failure hospitalization endocarditis and death.     Among 920 patients followed for a mean of 90.3 ± 5.1 years, 21% (191) developed cardiovascular events. Arrhythmia and aortic complications were most frequent cardiovascular events. A substantially higher incidence of events was observed in patients with the presence of a bicuspid aortic valve, mechanical heart valve (n= 60; 49 aortic, 5 mitral and 6 both), and/or Turner syndrome.   Overview of cardiovascular events     In univariate analysis, older age at CoA repair, bicuspid aortic valve increased BMI and elevated LV mass index [LVH defined on echocardiography as LV mass index > 115 G/m2 in Males and > 95 G/m2 in females] and were associated with increased risk, whereas female gender was associated with decreased risk. In multivariate analysis LV mass index and older age at repair (>10 years) were identified as independent risk factors for the occurrence of cardiovascular events.   Estimated early risk of cardiovascular events:     Factors associated with risk of cardiovascular events     LVH and Cardiovascular Events     Mortality occurred in 42 patients with 57% (24) attributed to cardiovascular events. Mortality was 3.3 times higher than the age, sex matched Dutch general population. It remained higher than general population even for patients with isolated CoA without other congenital heart defects or mechanical valves.   Overall Survival     Conclusion: Cardiovascular events are common after CoA repair. While aortic complications and arrhythmias are the most common cardiovascular events, late age at repair, and elevated LV mass index are independent risk factors. There is 3.3 fold mortality increase after CoA repair when compared to the matched general population. There data support preventive strategy implementations.