December

Effect of Losartan or Atenolol on Children and Young Adults With Bicuspid Aortic Valve and Dilated Aorta

Effect of Losartan or Atenolol on Children and Young Adults With Bicuspid Aortic Valve and Dilated Aorta. Flyer JN, Sleeper LA, Colan SD, Singh MN, Lacro RV. Am J Cardiol. 2020 Dec 29:S0002-9149(20)31400-4. doi: 10.1016/j.amjcard.2020.12.050. Online ahead of print. PMID: 33383013   Take Home Points: In children and young adults with bicuspid aortic valve and dilated ascending aorta, in this retrospective, single centre, non-placebo controlled, non-blinded and non-randomised study of 41 patients: Treatment with losartan or atenolol over an average three year period reduced aortic root and ascending aorta Z-scores. Both resulted in an apparent reduction in absolute aortic diameter growth rates. Losartan or atenolol may reduce proximal aortic growth rates in young patients with bicuspid valve aortic aortopathy.   Commentary from Dr Simon MacDonald (London, UK), section editor of ACHD Journal Watch: It is established that beta-blockade and angiotensin II blockade protects against aortic dilatation in Marfan’s syndrome but their role and possible effectiveness in other types of aortopathy is unclear. The authors studied whether atenolol or losartan prophylaxis reduces aortic dilatation in children and young adults with bicuspid aortic valve and dilated ascending aorta. In this group, severe dilatation is associated with risk of dissection and death.   They reviewed patients with bicuspid aortic valve and aortic dilatation (aged 1 day to 29 years) at Boston Children’s Hospital over the time period 1990-2018. Their hospital protocol recommended medical prophylaxis with losartan or atenolol for patients with bicuspid aortic valve and severe aortic root or ascending aorta dilatation. Patients were identified via their hospital database with BAV and aortic root or ascending aorta diameter with z-score ≥ 4SD and/or absolute diameter ≥ 4cm, and history of prophylaxis with losartan or atenolol. Patients with other congenital heart disease, apart from coarctation, or known connective tissue disorders were excluded.   The primary outcome analysed was the annual rate of change in maximal aortic root and ascending aorta z-scores (SD/yr) compared with those before treatment. Mean changes over time in aortic diameter and BSA adjusted z-scores for the treatments were analysed using a mixed effects linear regression model.   They included gender as a subgroup, in addition to age at initiation (<15 yrs. and ≥ 15years), aortic z-score, coarctation surgery, presence or absence of moderate aortic insufficiency or stenosis. Forty-one patients were included in the analysis, 27 in the losartan group and 18 in the atenolol (4 patients included in both groups as received each drug at different times) with similar baseline characteristics (Table 1A). Median treatment duration was 3.1 years for losartan (IQR 2.4, 6.0) and 3.7 for atenolol (IQR 1.4,6.6) with mean age of initiation of therapy 14.2±5.1 and 15±4.9 years respectively.     Treatment was associated with decreases in aortic root and ascending aorta z-scores (SD/yr) for losartan and atenolol (pre- vs post-treatment) with: Losartan, n=27: Aortic root: +0.06± 0.02 pre vs -0.14±0.03 post, p<0.001 Ascending aorta: +0.2±0.03 pre vs -0.09±0.05 post, p<0.001   Atenolol, n=18: Aortic root: +0.07±0.03 pre vs -0.02±0.04 post, p<0.01 Ascending aorta: +0.21±0.04 pre vs -0.06±0.006, p<0.001   There was a decrease in absolute growth rate (cm/year) for all comparisons (p≤0.02) too.     There were no deaths, with four patients in the losartan group and five in the atenolol having surgery. This was for Sinus of Valsalva fistula (1), aortic size (2), and progressive aortic regurgitation (6). Seven had aortic valve repair/replacement and 8 had replacement/reduction of the aortic root and or ascending aorta.   Patients were not randomised, it was a single centre retrospective study, variable drug dosing, and unblinded echo assessment were potential limitations. In terms of subgroup analysis, there were a small number of patients assessed, and coarctation surgery, aortic valve dysfunction and timing of growth spurts in male/female patients were potential confounders. The authors conclude that additional large clinical studies are warranted with these medications to confirm possible effect and help decrease the rate of serious aortic events during adulthood.   

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Pulmonary Arterial Hypertension Associated with Congenital Heart Disease in Adults over the Age of 40 Years

Pulmonary Arterial Hypertension Associated with Congenital Heart Disease in Adults over the Age of 40 Years Maurer SJ, Stöckemann K, Pujol C, Hörer J, Ewert P, Tutarel O. J Clin Med. 2020 Dec 17;9(12):4071. doi: 10.3390/jcm9124071. PMID: 33348628 Free PMC article.   Take Home Points: In patients over age 40, with congenital heart disease and pulmonary hypertension, a quarter died during the follow up period of 4 years. Creatinine and NT pro-BNP were the only factors significantly associated with the primary end-point. Commentary by Dr. Helen Parry (Leeds, UK), section editor of ACHD Journal Watch: There is currently relatively little research looking at the natural history and prognostic factors in pulmonary arterial hypertension in older adults with congenital heart disease. This study focuses on this cohort of patients over 40 years of age.   All patients at the German Heart Centre in Munich with a diagnosis of congenital heart disease and pulmonary arterial hypertension (PAH) above the age of 40 were included. Pulmonary arterial hypertension was diagnosed based on echo, MRI and/ or catheter studies. The patients were sub-categorised as: Shunt lesions Complex congenital heart disease Segmental PAH, i.e. patients with major aorto-pulmonary collaterals (MAPCAs) The primary end-point was all-cause mortality. Variables examined included: NYHA score Echo assessment of left and right ventricular function Presence of arrhythmia NTpro-BNP Creatinine Arrhythmia Presence of Down’s syndrome Use of advanced PAH therapies. Univariate analysis was used to assess whether these variable were associated with death (Students’ t test for continuous variables and Chi squared test for categorical variables). Multivariate analysis by Cox proportional hazard regression modelling was used to assess their relative significance. P-value <0.05 was classed as significant.   Results: Sixty-five patients were included; 70.8% had a shunt lesion, 18.5% complex CHD and 10.8% segmental PAH. Median follow-up was 4.2 years. Atrial arrhythmia occurred in 23.1% and ventricular arrhythmia in 9.2%. Sixteen patients (24.6%) died during the follow up period. Univariate analysis showed an association between both creatinine and NT-pro-BNP and all-cause mortality:   VariableUnivariate HR (95%CI)Univariate p-valueMultivariate HR (95% CI)Multivariate p-value Creatinine12.76 (2.05–79.32)0.006316.28 (2.23–118.690.0059 NT pro-BNP3.54 (1.08–11.64)0.0374.08 (1.16–14.41)0.0289   Conclusions: A quarter of the patients above 40 years of age with combined congenital heart disease and PAH died during the follow up period. Creatinine and NT pro-BNP were the only factors significantly associated with the primary end-point.   Positive aspects of the study: There is very little in the literature about this group of patients so this study was a useful contribution. The identified predictors of poor prognosis, namely, raised creatinine and raised NT pro BNP can be relatively easily measured routinely in most centres. May contribute towards counselling regarding in certain patients. Negative aspects of the study: Small sample size. The majority of patients had shunt lesions so it is difficult to extrapolate the results to the other groups as they were relatively under-represented, could survival be worse or better in these groups? The sample sizes were too small to draw confident conclusions. The study does not really help to guide treatment in these patients. The questions are posed: should we try to improve creatinine and NT pro-BNP in these patients and will this improve their prognosis? NT pro-BNP is generally improved by increasing heart failure therapies, many of which are nephrotoxic so likely to increase creatinine. Follow up period varied significantly from 1.2 years to 7 years.  

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Patients with Single-Ventricle Physiology over the Age of 40 Years

Patients with Single-Ventricle Physiology over the Age of 40 Years Pujol C, Schiele S, Maurer SJ, Hock J, Fritz C, Hager A, Ewert P, Tutarel O. J Clin Med. 2020 Dec 18;9(12):4085. doi: 10.3390/jcm9124085. PMID: 33352831 Free PMC article   Take Home Points: Patients over 40 years with single ventricular physiology are burdened with morbidity and mortality. This group of patients frequently has arrhythmia and required cardioversion, pacemakers, or antiarrhythmic medications. The presence of renal disease is associated with mortality.   Commentary from Dr. M.C. Leong (Kuala Lumpur, Malaysia), section editor of ACHD Journal Watch: The survival of single ventricular hearts has improved over the years owing to improved surgical techniques, understanding of the underlying physiology and follow-up care. However, the long-term morbidities and mortality remain unresolved and is largely due to the limitations of the Fontan circulation. These morbidities become more evident as the patients age.   In this article, Pujol and colleagues reported on the outcome data from their cohort of patients with single ventricle physiology above the age of 40 years. In this cohort, 49 patients (19 female, mean age 49.2 ± 6.4 years, median follow up duration: 4.9 years, IQR: 1.8–8.5) were identified. Baseline characteristics were as tabulated in Table 1.   Strikingly, although over 80% of these patients were in NYHA functional class I-II, 35 (71.4%) of patients had a prior hospital admission for heart failure. Many of them were plagued with comorbidities. Arrhythmias were a frequent challenge. 23 (53%) of these patients had lost sinus rhythm; amongst them, 13 patients required pacemakers. Another 8 patients required pacemakers during the follow-up period. On follow-up, 9 (18.4%) of patients underwent electrophysiological procedures. Cardioversion was required in 20 (40.8%) patients, amongst them, 14 patients required multiple episodes of cardioversion. In relation to the frequency of atrial arrythmias, the type of Fontan circulation was not specified (Atriopulmonary, lateral tunnel or extra-cardiac conduit). Arrhythmias in patients with severely dilated atria are notoriously difficult to control and often they affect the quality of lives of these patients despite medications.   During the follow-up, there were 10 (20.4%) mortalities. The authors subsequently analysed the factors associated with death in this cohort (Table 2). On univariate analysis, renal disease and liver cirrhosis were predictors of all-cause mortality. However, on multivariate analysis, only renal disease (HR: 12.5, 95% CI: 1.5–106.3, p = 0.021) remained as an independent predictor (Figure 1). End organ damage has commonly been found to be a good surrogate marker for disease progression. The cause for end organ damage may be attributed to the chronic elevation of systemic venous pressure, low perfusion to the end organs due to chronic heart failure and possibly, repeated episodes of end organ injuries during acute heart failure which may be triggered by acute arrhythmias, surgeries or infections. Renal disease is a useful predictor of mortality and thus aids in the planning of follow-up and risk stratification of these patients.       In summary, this is a study looking at the outcome of a special cohort of older patients with Fontan palliation. Although this data highlights the burden of morbidities and mortality, it is difficult to draw the same conclusion to the younger cohort who has mostly undergone the extracardiac type of Fontan palliation which, hopefully, has a low burden of arrhythmia. On the other hand, this younger cohort of Fontan population may have a poorer substrate i.e., heterotaxies and hypoplastic left heart syndromes, which may give rise to a different set of morbidities and mortality risk.    

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Pregnancy Outcomes in Women After Arterial Switch Operation for Transposition of the Great Arteries: Results From ROPAC (Registry of Pregnancy and Cardiac Disease) of the European Society of Cardiology EURObservational Research Programme

Pregnancy Outcomes in Women After Arterial Switch Operation for Transposition of the Great Arteries: Results From ROPAC (Registry of Pregnancy and Cardiac Disease) of the European Society of Cardiology EURObservational Research Programme Tutarel O, Ramlakhan KP, Baris...

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Method comparison of HPLC-ninhydrin-photometry and UHPLC-PITC-tandem mass spectrometry for serum amino acid analyses in patients with complex congenital heart disease and controls

Method comparison of HPLC-ninhydrin-photometry and UHPLC-PITC-tandem mass spectrometry for serum amino acid analyses in patients with complex congenital heart disease and controls Michel M, Salvador C, Wiedemair V, Adam MG, Laser KT, Dubowy KO, Entenmann A, Karall D,...

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