Adult Congenital Heart Disease

Assessment and Implications of Right Ventricular Afterload in Tetralogy of Fallot. Egbe AC, Taggart NW, Reddy YNV, Sufian M, Banala K, Vojjini R, Najam M, Osman K, Obokata M, Borlaug BA. Am J Cardiol. 2019 Dec 1;124(11):1780-1784. doi: 10.1016/j.amjcard.2019.08.035. Epub 2019 Sep 9. PMID: 31586531 Similar articles Select item 30772131   Take Home Points: In adult patients with repaired tetralogy of Fallot (TOF), higher right ventricle systolic pressure (RVSP) is associated with worse prognosis including a higher risk of death or transplant. However, there was no such association with right ventricle outflow tract (RVOT) obstruction severity. In this study, there was good correlation between invasively measured and Doppler derived RVSP. Commentary from Dr. Maan Jokhadar (Atlanta GA), section editor of ACHD Journal Watch: Repaired TOF patients commonly have residual RVOT obstruction and increased right ventricle (RV) pressure overload. This is in addition to the increased risk of pulmonary valve regurgitation after repair and right ventricle volume overload. Dr. Egbe and colleagues from Mayo Clinic in Rochester, Minnesota performed a retrospective cohort analysis of 266 adult TOF patients who had contemporaneous echocardiography and cardiac catheterization (within 48 hours) between 1990 and 2015. Patients with aortopulmonary collaterals were excluded. The mean age was about 35 and the mean follow-up with just under 13 years. In this study, invasively measured RVSP was used as an index of RV afterload, which can increase as a result of any number of factors that include RVOT obstruction, pulmonary artery vascular obstruction, pulmonary vascular resistance, and increased left heart filling pressure. Study participants were divided into 2 groups based on RVOT gradient of less or more than 36 mmHg. About 66% (175 patients) had significant RVOT obstruction and the rest did not. During a follow-up period of almost 13 years, there was no significant mortality difference between patients with and without RVOT obstruction: 27/175 patients died in the RVOT obstruction group and 8/91 patients died in the no RVOT obstruction group. Of the 35 patients who died, right heart failure was the cause in 14, sudden-death in 11, sepsis with multi organ system failure in 3, postoperative death in 4, major bleeding in 2, and 1 died of unknown causes. There were 4 patients who had heart transplant. In this study, there was good correlation between invasively measured and Doppler derived RVSP. In adult repaired TOF patients, higher RVSP, as a marker of RV afterload, was independently associated with death and heart transplant, whether assessed invasively or non-invasively. However, there was no such association with RVOT obstruction. Thus, increased RV pressure overload from any cause is a marker of worse prognosis in repaired TOF patients. Further study is needed to determine if reducing RV pressure overload improved outcomes. The results of the study bolster the notion that elevated RVSP is helpful in the risk stratification and decision-making regarding pulmonary valve intervention for patients with repaired TOF and pulmonary regurgitation. However, further study is needed.  

Fontan protein-losing enteropathy is associated with advanced liver disease and a proinflammatory intestinal and systemic state. Rodríguez de Santiago E, Téllez L, Garrido-Lestache Rodríguez-Monte E, Garrido-Gómez E, Aguilera-Castro L, Álvarez-Fuente M, Del Cerro MJ, Albillos A. Liver Int. 2020 Jan 8. doi: 10.1111/liv.14375. [Epub ahead of print] PMID: 31912956 Similar articles Take Home Points: Fontan patients with PLE demonstrated more severe liver damage and cardiac impairment, and greater systemic inflammation, intestinal inflammation and intestinal permeability than those without PLE. Timely reminder that liver assessment and close surveillance is essential in all Fontan patients, and especially those with PLE. Faecal calprotectin is complementary to faecal alpha-1-antitrypsin and may be useful as a biomarker for the diagnosis and follow-up of Fontan PLE. Data originates from an observational single-centre case-control study (n=29). Commentary from Dr. Timothy Roberts (Melbourne, Australia), section editor of ACHD Journal Watch: Background Protein-losing enteropathy (PLE) affects 3 – 18 % of patients after a Fontan operation, and is thought to be contributed by factors including elevated central venous pressure and inflammation. Aims of this study: to investigate in patients with Fontan circulation and PLE: a. the presence of intestinal and systemic inflammation; b. the relationship between PLE and severity of liver and cardiac damage. Methods All Fontan subjects diagnosed prospectively with PLE were included. PLE was defined as a 24 hours alpha-1-antitrypsin faecal clearance value above 27 mL/day. Exclusion criteria were coexisting inflammatory bowel disease, coeliac disease or gastrointestinal infection. Controls were matched at a 1:1 ratio by age (±2 years) and Fontan surgery procedure (atriopulmonary vs total cavopulmonary). Initial assessment included a structured medical interview, physical examination, blood and faeces tests, abdominal Doppler-ultrasonography, liver elastography, abdominal angio-magnetic resonance imaging (MRI) or computed tomography (CT) scan when MRI was contraindicated, and echocardiography. A cardiac MRI and cardiac haemodynamic study were also performed when clinically indicated. Results Of 61 subjects, 15 had PLE (24.6 %) with one excluded following diagnosis of coeliac disease. Fifteen control Fontan patients were included (see Figure 1, below). Faecal calprotectin was significantly increased in the PLE group (80 vs 30 ug/g, P < 0.001; Figure 2). Serum I-FABP, used as a marker of intestinal barrier disruption, was elevated in PLE (9 vs 5 ng/ml, P = 0.019), while pro-inflammatory cytokines TNF-alpha and IL-6 were also elevated in the PLE cohort (Figure 3). Cardiac index was lower in PLE subjects in the hemodynamic study (2.54 vs 4.25 L/min/m2, P = .016), lower ventricular ejection fraction on cardiac MRI (58.5% vs 63.5%, P = .04) and lower systemic oxygen saturation (93% vs 96%, P = .025). No difference in BNP was observed. No difference in routine liver function testing was observed (bilirubin, ALT, AST, GGT, ALP). Platelet count was lower, while liver stiffness was greater (25.4 vs 14.3 kPA; P < 0.001) in the PLE group. No cases of hepatocarcinoma were diagnosed. Conclusions Fontan patients with PLE demonstrated more severe liver damage and cardiac impairment, and greater systemic inflammation, intestinal inflammation and intestinal permeability than those without PLE. Faecal calprotectin is complementary to faecal alpha-1-antitrypsin and may be useful as a biomarker for the diagnosis and follow-up of Fontan patients diagnosed with PLE.  

Inspiratory muscle training did not improve exercise capacity and lung function in adult patients with Fontan circulation: A randomized controlled trial. Fritz C, Müller J, Oberhoffer R, Ewert P, Hager A. Int J Cardiol. 2020 Jan 9. pii: S0167-5273(19)33852-5. doi: 10.1016/j.ijcard.2020.01.015. [Epub ahead of print] PMID: 31992463   Take Home Points: Daily IMT for a 6 month period did not improve exercise and lung capacity and lung volumes in Fontan patients. Daily IMT for 6 months in adult patients with Fontan was associated with an increase in O2 saturation at rest. Larger studies are warranted in order to gain more insight into the mechanisms of exercise training and the Fontan physiology. Commentary from Dr. Soha Romeih (Aswan, Egypt), section editor of ACHD Journal Watch: Background: In Fontan patients, due to the hemodynamic limitations of an absent sub-pulmonic chamber, pulmonary arterial and systemic venous blood flow are strongly affected by modest intrathoracic pressure shifts, since ± 30% of flow in the systemic venous pathway is driven by respiration. In patients with Fontan circulation, blood flow in the IVC is increased during inspiration, enhancing the systemic venous blood return into the lungs considerably. Young adults with Fontan circulation show respiratory and skeletal muscle weakness, and higher prevalence of respiratory muscle dysfunction, comparable to adults with advanced heart failure. In a recent study in children with Fontan circulation, daily inspiratory muscle training (IMT) of six weeks improved inspiratory muscle strength and ventilatory efficiency in a cardiopulmonary exercise test (CPET). It is therefore reasonable that an individually adjusted IMT in adult patients with Fontan circulation improves parameters of ventilation and exercise capacity. The aims of the current study were to investigate the effect of a telephone-supervised, daily inspiratory muscle training for 6 months on exercise capacity and on lung volumes in adult patients with Fontan circulation. Methods Study subjects 42 patients (50% female; 30.5 ± 8.1 years; age 18 to 51 years old) out of 209 eligible patients participated from January 2017 until October 2018. After baseline assessments (visit 1), consisting of a lung function test (LFT) and a CPET, 42 patients were randomized into either an intervention group (IG, n = 20) or control group (CG, n = 22). The IG started performing a telephone-supervised, daily IMT until six months follow-up (visit 2). The daily intervention was performed with an inspiratory resistive training device (POWER breathe International Ltd., Southam, UK). Within the first six months after baseline evaluation the CG continued their usual activities and did not get any treatment. At the six months follow-up (visit 2) this group started IMT under the same conditions, including weekly telephone supervision till 12 months re-evaluation (visit 3). To assess the sustainability of the training program, the IG was asked to continue performing IMT without weekly telephonic-supervision until 12 months reevaluation (visit 3). This independent six-months IMT period of the CG was performed from 12 months follow-up until 18 months re-evaluation (visit 4). (Figure 1) The study consisted of three visits for the IG and four visits for the CG, where a CPET and a LFT were performed, respectively. All tests were implemented by the same experienced sports scientist. Inspiratory muscle training (IMT) After baseline evaluation patients were instructed by an experienced sports scientist in term of the IMT. Patients were instructed to begin the inhalation phase with diaphragmatic breathing and to continue inhaling by expanding the rib cage. Incorrect breathing and malposition were corrected immediately. Patients used an inspiratory resistive training device for three sets with 10–30 repetitions once daily. During the second 6 months training period, patients were instructed to continue the IMT independently, since no telephone supervision was implemented. Both groups performed IMT under the same conditions. Measurement of exercise capacity Incremental symptom-limited CPET until exhaustion. Gas exchange and ventilation were measured via a breath-by-breath gas exchange analysis. Peak oxygen uptake (VO2 peak) was calculated as the highest mean O2 consumption obtained during any 30-second time interval. Compliance criteria for a valid CPET were achieved when either respiratory exchange ratio (RER) was ≥1.05, or peak heart rate was ≥85%. Cyanotic patients (oxygen saturation b 90% at rest or at peak exercise) were rarely able to reach the above-mentioned thresholds, however they were included in the study, independent of those criteria. Measurement of lung function Forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and the FEV1/FVC ratio were performed. Results: Exercise capacity At 6 months re-evaluation both groups had not improved their VO2 peak and VO2 peak predicted, without any significant difference between IG and CG. Additionally, no significant difference was found between the IG and the CG concerning ventilatory efficiency. The only significant result was an increase of O2 saturation at rest in the IG in comparison to the CG after six months IMT. These results indicate an enhancement of hypoxic pulmonary vasoconstriction resulting in an improvement in ventilation/perfusion matching, which favors systemic oxygen delivery by the constriction of intrapulmonary arteries reacting to alveolar hypoxia. Another plausible mechanism could be a reduction in chronic atelectasis following IMT. Hence IMT may improve blood flow of the lungs. Lung function After 6 months of IMT, no significant changes could be observed between the IG and the CG concerning FVC and FVC predicted. Further, FEV1 and FEV1 predicted did not change significantly after IMT between the IG and CG. Conclusions Six months of weekly telephone-supervised, daily IMT could not improve exercise and lung capacity in adult patients with Fontan circulation. According to current evidence, beneficial effects of IMT in adult patients with Fontan circulation cannot be verified. Therefore, larger studies are warranted in order to gain more insight into the mechanisms of exercise training and the Fontan physiology.  

Fontan-associated nephropathy: Predictors and outcomes. Khuong JN, Wilson TG, Grigg LE, Bullock A, Celermajer D, Disney P, Wijesekera VA, Hornung T, Zannino D, Iyengar AJ, d'Udekem Y. Int J Cardiol. 2020 Jan 10. pii: S0167-5273(19)34728-X. doi: 10.1016/j.ijcard.2020.01.014. [Epub ahead of print] PMID: 31955974   Take Home Points: 20% of patients with Fontan circuits have mild to moderate renal dysfunction as per eGFR. Atrio-pulmonary Fontan and the absence of a prior bidirectional were the only predictors of renal dysfunction In this cohort, renal dysfunction did not impact the outcomes of death, cardiac transplantation or Fontan failure. Commentary from Dr. Blanche Cupido (Cape Town, South Africa), section editor of ACHD Journal Watch: Although nephropathy is a known complication of a Fontan circuit, not much data is available in contemporary literature on this topic. This study from the Australia and New Zealand Fontan Registry aimed to ascertain the prevalence of nephropathy, identify its predictors and characterize their long term outcomes in young adults with Fontan circuits. Patients >age 16 with Fontan circuits were included if they had a serum creatinine measurement when between the ages of 16 and 25. Those with primary renal diagnoses, those who underwent Fontan take-downs, received heart transplantation or died before age 16, were excluded. Baseline renal function was assessed by glomerular filtration rate (GFR) as per the Modification of Diet in Renal Disease (MDRD) equation. Renal dysfunction was defined as a GFR < 90ml/kg/min/1.73m2. The primary end-point for Fontan failure was death, heart transplantation, plastic bronchitis, protein losing enteropathy, Fontan take-down and NYHA III-IV. The secondary outcome was chronic kidney disease – GFR < 90ml/kg/min/1.73m2. A total of 328 patients were included. Fifty-two percent were male and the mean age was 26 years. The prevalence of renal dysfunction was 20% (n=67). Most had mild renal dysfunction, though 1% (3 patients) had moderate renal dysfunction with a GFR < 60ml/kg/min/1.73m2. The following factors were associated with increased renal dysfunction on univariate analysis: Atrio-pulmonary Fontan (AP Fontan) – OR 2.22 (95% CI 1.11-4.30, p=0.024) Absence of prior bidirectional cavo-pulmonary shunt – OR 2.23 (95% CI 1.28-3.98, p=0.005) This did not hold for multi-variate analysis though. Two patients in the renal dysfunction group (2%) and 19 (7%) of the non-renal dysfunction group died during follow-up. From Figure 1 below, it is evident that fewer deaths occurred in the renal dysfunction group (2/67 deaths vs 9/261 deaths) Ten year survival for the renal dysfunction group was 96% compared to 89% in the non-renal dysfunction group. (p=0.1) No independent risk factors for mortality were identified. Figure 2 below shows that the 10-year freedom from death and transplant for the renal dysfunction and no renal dysfunction groups were 96% and 87% respectively (p=0.05) Fontan failure occurred in 12% of patients (n=38) over a 7 year follow-up period. There was no difference in the prevalence of Fontan failure between those with and without renal dysfunction. Ten year freedom from Fontan failure was 82.5% in the renal dysfunction group and 81% in the no renal dysfunction group (p=0.84) – see figure 3 below. Independent risk factors for Fontan failure were right atrial isomerism and developing >moderate ventricular systolic dysfunction. Over an 8 year follow-up period, no significant differences in mean eGFR were found in the group who had renal dysfunction at the outset (eGFR 78 vs 80ml/kg/min/1.73m2, p=0.4). The group with normal renal function initially, did show a decline in eGFR (120 to 108ml/kg/min/1.73m2, p<0.001).