Systemic Ventricular Function Research Articles

Sacubitril/valsartan for heart failure in adults with complex congenital heart disease

BackgroundHeart failure is an important cause of morbidity and mortality in adults with congenital heart disease (ACHD). Sacubitril/valsartan is an established treatment for heart failure with reduced ejection fraction due to acquired cardiovascular disease. Data in adults with complex congenital heart disease (CHD) is lacking. MethodsRetrospective study of ACHD patients with CHD of moderate/severe complexity and heart failure under treatment with sacubitril/valsartan. Clinical data was retrieved from medical records. ResultsAltogether, 23 patients (mean age 41.2 ± 11.9 years, female 17.4%) were included. A systemic right ventricle was present in 12 pat. (52.2%), a single ventricle physiology in 4 (17.4%), and a systemic left ventricle in 7 (30.4%). During a median follow-up of 221 days [IQR 79–430], systemic ventricular function (p = 0.88) and functional status according to New York Heart Association class (p = 0.38) did not improve. While NT-proBNP levels did not change significantly under treatment (2561 ± 2042 ng/l vs. 1938 ± 1524 ng/l, p = 0.20), creatinine levels increased (1.14 ± 0.52 mg/dl vs. 1.35 ± 0.74 mg/dl, p = 0.002). Systolic (110 ± 15 mm Hg vs. 103 ± 14 mm Hg, p = 0.02) and diastolic blood pressures (68 ± 10 mm Hg vs. 61 ± 12 mm Hg, p = 0.01) were reduced under therapy. Five patients discontinued therapy, four of these due to side effects. ConclusionIn this small group of complex ACHD patients with heart failure, treatment with sacubitril/valsartan did not improve systemic ventricular function or functional status. Renal function needs close surveillance.

High-risk Fontan completion patients achieve low perioperative risk and benefit from cavopulmonary connection 7 years out†.

Our unit has pursued Fontan completion in all patients except those with immobility or combined poor ventricular function and high pulmonary artery pressures. We assessed retrospectively whether conventional high-risk criteria would predict patients with a poorer outcome. One hundred and thirty-three consecutive children who underwent extracardiac Fontan completion (2004-2012) had their outcomes recorded (mean follow-up of 7 years). Three groups were analysed: those with 1 of 6 historical risk factors (outside 6 commandments), those with 1 of reduced systemic ventricular function or pulmonary artery pressure >15 mmHg (outside 2 commandments) versus those with no contraindications. The Fischer's exact test examined frequency differences, with the χ2 test to look for outcome associations. There were no differences in postoperative complication rates between the outside 6 commandments (n = 105) or outside 2 commandments (n = 49) versus the low-risk no-contraindication group (n = 28): arrhythmias [18% (P = 0.3) or 18% (P = 0.3) vs 25%], infection [22% (P = 0.6) or 33% (P = 0.2) vs 21%], cerebrovascular accident [6% (P = 0.5) or 10% (P = 0.3) vs 4%], length of stay [20 days (P = 0.4) or 23 days (P = 0.2) vs 21 days] and duration of chest drainage (P = 0.5). There was 1 predischarge mortality in each group. Long term, the majority of patients in each group had suitable haemodynamics for fenestration closure [95% (P = 0.7) or 95% (P = 0.7) vs 92%]. Long term, there was no difference in the rate of arrhythmias [11% (P = 0.5) or 12.5% (P = 0.3) vs 7%], protein-losing enteropathy [1% (P = 0.1) or 2% (P = 0.3) vs 7%] or moderate or more ventricular dysfunction on echocardiography [2% (P = 0.7) or 4% (P = 0.7) vs 4%]. Notably, there was a higher rate of catheter reinterventions in the high-risk groups [22% (P < 0.05) or 24% (P < 0.05) vs 7%]. The medium-term benefits of Fontan completion can be achieved for high-risk patients, suggesting that historical selection criteria should be re-examined.

THE USE OF OXYGEN UPTAKE EFFICIENCY SLOPE FOR RISK STRATIFICATION OF PATIENTS WITH D TRANSPOSITION FOLLOWING ATRIAL SWITCH PROCEDURE

Patients with d-transposition and atrial switch repair are at risk for adverse outcome (ADV) due to decline in systemic right ventricular function. Exercise testing in adults with a systemic left ventricle and heart failure have identified prognostic values for ADV including oxygen consumption (VO2

Clinical Evaluation of Exercise Capacity in Adults with Systemic Right Ventricle.

The right ventricle provides systemic circulation in individuals with congenitally corrected transposition of the great arteries (CCTGA) and in those with complete transposition who have had an atrial switch repair (DTGA). The aim of this study was to evaluate how the systemic right ventricle adapts to increased workload and oxygen demand during exercise. From November 2005 through December 2015, 3,358 adult patients with congenital heart disease were treated at our institution; we identified 48 (26 females, 22 males; median age, 25.4 ± 8.1 yr) who met the study criteria; 37 had DTGA and atrial switch repair, and 11 had CCTGA. We studied their echocardiographic and cardiopulmonary exercise test results. A control group consisted of 29 healthy sex- and age-matched volunteers. On exercise testing, oxygen uptake at anaerobic threshold, peak oxygen uptake, peak heart rate, and percentage of maximal heart rate were significantly lower in the group with systemic right ventricle than in the control group (all P <0.001); in contrast, the peak ventilatory equivalent for carbon dioxide was higher in the study group (P=0.013). Impaired systemic right ventricular function reduced peak oxygen uptake. The peak heart rate was lower in the CCTGA group than in the DTGA group. Our results indicate that reduced exercise capacity is related to impaired systemic right ventricular function, severe tricuspid valve regurgitation, and chronotropic incompetence. There was no correlation between cardiopulmonary exercise test results and time after surgery. Chronotropic efficiency is lower in individuals with CCTGA than in those with DTGA.

Pregnancy outcomes and mid-term prognosis in women after arterial switch operation for dextro-transposition of the great arteries – Tertiary hospital experiences and review of literature

ObjectiveArterial switch operation (ASO) for dextro-transposition of the great arteries (d-TGA) has gradually replaced the atrial switch operation and has become the standard operation. To date, the outcomes of pregnant women with d-TGA after this new operation have not been investigated. In this study, we investigated the impact of ASO on pregnant outcomes and mid-term prognosis in women with d-TGA and compared with the atrial switch operation through the literature review. Methods and resultsThere were 20 pregnancies in 10 women with d-TGA after ASO and 6 resulted in abortion. Among 14 successful pregnancies in 10 women, 11 pregnancies achieved the term delivery and 3 pregnancies, including 1 twin pregnancy, resulted in preterm labor. Maternal cardiovascular events occurred in 4 (heart failure and arrhythmias in 3 and arrhythmia in 1), and all were controllable with medications. Risk factors for the peripartum cardiac events were older age at ASO and delivery, and higher concentration of brain natriuretic peptide (BNP) at first trimester (p<0.05). In 7–60 month-follow-up after delivery, no case showed deterioration of functional class and systemic ventricular function. According to the literature review, women after ASO demonstrated a better prognosis than those after the atrial switch operation. ConclusionsThe majority of women with d-TGA after ASO tolerated pregnancy and delivery well. The older age at ASO, an elderly pregnancy, and higher BNP levels at the first trimester were possibly risk factors of peripartum cardiovascular events among the group. The literature reviews and this study may indicate the advantage of systemic left ventricle compared with systemic right ventricle in long-term outcomes after delivery.

Long-term clinical outcomes of valsartan in patients with a systemic right ventricle: Follow-up of a multicenter randomized controlled trial

ObjectivesIn the VAL-SERVE (Valsartan in Systemic Right Ventricle) trial, three-year valsartan treatment improved systemic ventricular function only in symptomatic patients with congenitally or with an atrial switch corrected transposition of the great arteries. The aim of the current study was to investigate the longer-term clinical outcomes after valsartan treatment. MethodsFrom 2006 to 2009, 88 adults were randomly allocated 1:1 to either valsartan or placebo for three consecutive years. Endpoints were defined as overall survival and freedom from clinical events (arrhythmia, heart failure, tricuspid valve surgery, death). ResultsCardiac drug use and median follow-up after trial close-out (8.3 years) was similar between the randomization groups. Six patients (valsartan n = 3, placebo n = 3) died in 364 and 365 person-years (P = 0.999). No difference in the composite or separate clinical endpoints was found between the randomization groups, with corresponding long-term event-free survival rates of 50% and 34%. Nevertheless, in symptomatic patients valsartan significantly reduced the risk for events compared to placebo (HR 0.37, 95% CI 0.17–0.92). Analysis for repeated events and on-treatment analysis with any renin-angiotensin-aldosterone-system-inhibitor did not alter these results. ConclusionsValsartan treatment in systemic RV patients did not result in improved survival at longer-term follow-up, but was associated with decreased risk of events in symptomatic patients.

67. Birthweight in pregnancies complicated by maternal heart disease

Objective To assess the mean and centile birthweight distribution in women with various groups of heart disease compared with controls. Methods Data on birthweight and gestational age at birth (⩾24 weeks gestation) were collected about women with known heart disease (both congenital and acquired) from seven specialist UK maternity units. Women were assigned to one of 16 groups according to their cardiac lesion. Whenever possible, data on two controls delivering before and after the index cases was also collected. Birth weight percentiles (corrected for gestational age, sex and parity) were calculated using the Aberdeen norms. Using multivariate regression, we also assessed the impact of beta blockers, maternal hypoxemia maternal saturations ( Results 1321 pregnancies in women with heart disease and 2307 controls were studied. All groups of women with heart disease had lower mean centile birthweight than controls, significantly so in 10 groups, the biggest effect being seen in women with Fontan circulation, pulmonary hypertension, prosthetic heart valves, systemic right ventricle, Marfan’s syndrome, repaired tetralogy of Fallot, and cardiomyopathy (in that order). Beta blockers, low maternal oxygen saturation, and impaired systemic ventricular function were also associated with significantly lower centile birthweights.Following multivariate regression; mean birthweight with beta blockers was 3116.7 g (SD 700.02) cf 3354.7 g (SD 539.06) without beta blockers, a difference of 238.1 g (p Conclusion Our findings identify specific groups of women with heart disease at risk of having a small baby who therefore need close surveillance of fetal growth.

P5478Hepatitis C virus positivity adversely affects systemic ventricular function and long-term prognosis in patients with adult congenital heart disease

P5478Hepatitis C virus positivity adversely affects systemic ventricular function and long-term prognosis in patients with adult congenital heart disease

Implantable cardioverter defibrillator therapy in grown-up patients with transposition of the great arteries-role of anti-tachycardia pacing.

Grown-up patients with surgically corrected dextro-transposition of the great arteries (dTGA) as well as patients with congenitally corrected transposition of the great arteries (ccTGA) carry a high risk of ventricular arrhythmias. Data regarding implantable cardioverter defibrillator (ICD) therapy and efficacy of anti-tachycardia pacing in these patients is limited. Clinical data from a contemporary cohort of ICD carriers with atrial switch-corrected dTGA and burdened right ventricle or with ccTGA were obtained retrospectively from hospital records and patients were followed for additional 25 months prospectively. Clinical characteristics and ICD episode data were analyzed. Fourteen ICD carriers (8 male) with dTGA or ccTGA were included in the analysis. Four patients received the ICD for primary prevention based on severely reduced systemic ventricular function. The remaining patients had an ICD indication for secondary prevention. Cumulative follow-up added up to 113.5 patient-years. One patient died suddenly due to massive pulmonary embolism. One patient received a ventricular assist device. There were no arrhythmic deaths during the prospective follow-up period. Nine patients (64%) experienced a total of 177 ventricular tachyarrhythmias. Anti-tachycardia pacing was highly effective with 80% success rate in termination of arrhythmias. Five patients (36%) suffered from a total of 28 inappropriate ICD shocks for supraventricular tachycardia. In a contemporary cohort of ICD carriers with dTGA and ccTGA we observed a high proportion of appropriate ICD therapies for ventricular tachyarrhythmias. Over a period of up to 15 years almost two thirds of the patients received appropriate therapies. ATP was highly effective in our cohort and should therefore be programmed whenever possible.

Cardiac Ventricular Contractile Responses to Chronically Increased Afterload Secondary to Right Ventricular Outflow Obstruction in Patients With Tetralogy of Fallot

We examined the adaptive mechanism of the pulmonary ventricle (PV) in response to increased afterload secondary to pulmonary stenosis in tetralogy of Fallot (TOF, n = 47) and congenitally corrected transposition of the great arteries (cCTGA, n = 18), where the PV is morphologically different. We also elucidated the effects of such adaptation on systemic ventricular (SV) function. PV contractility, assessed by dp/dtmax, showed significant positive correlations with PV pressure (r = 0.82, p <0.01 for TOF and r = 0.78, p <0.01 for cCTGA) and pulmonary-to-systemic ventricular pressure ratio (r = 0.70, p <0.01 for TOF and r = 0.76, p <0.01 for cCTGA) in patients with both TOF and cCTGA. Notably, the slopes of these correlations were significantly higher in cCTGA than in TOF (p <0.01), suggesting enhanced contractile responses in cCTGA. Moreover, SV dp/dtmax showed significant positive correlations with PV dp/dtmax in patients with both TOF and cCTGA (r = 0.67, p <0.01 and r = 0.61, p <0.01, respectively), indicating positive ventricular-ventricular interaction. In this relationship, the slopes of correlations were significantly higher in TOF than in cCTGA (p = 0.024). These results, indicating different behaviors of PV contractile physiology and its interaction with the SV, may have important therapeutic implications when considering medical, catheter, and surgical interventions for pulmonary stenosis in these diseases. The results may also offer the potential for a new approach for improvement of prognosis, especially in cCTGA.

Adult Congenital Heart Disease with Pregnancy.

The number of women with congenital heart disease (CHD) at risk of pregnancy is growing because over 90% of them are grown-up into adulthood. The outcome of pregnancy and delivery is favorable in most of them provided that functional class and systemic ventricular function are good. Women with CHD such as pulmonary hypertension (Eisenmenger syndrome), severe left ventricular outflow stenosis, cyanotic CHD, aortopathy, Fontan procedure and systemic right ventricle (complete transposition of the great arteries [TGA] after atrial switch, congenitally corrected TGA) carry a high-risk. Most frequent complications during pregnancy and delivery are heart failure, arrhythmias, bleeding or thrombosis, and rarely maternal death. Complications of fetus are prematurity, low birth weight, abortion, and stillbirth. Risk stratification of pregnancy and delivery relates to functional status of the patient and is lesion specific. Medication during pregnancy and post-delivery (breast feeding) is a big concern. Especially prescribing medication with teratogenicity should be avoidable. Adequate care during pregnancy, delivery, and the postpartum period requires a multidisciplinary team approach with cardiologists, obstetricians, anesthesiologists, neonatologists, nurses and other related disciplines. Caring for a baby is an important issue due to temporarily pregnancy-induced cardiac dysfunction, and therefore familial support is mandatory especially during peripartum and after delivery. Timely pre-pregnancy counseling should be offered to all women with CHD to prevent avoidable pregnancy-related risks. Successful pregnancy is feasible for most women with CHD at relatively low risk when appropriate counseling and optimal care are provided.

The paradox of choice in the surgical management of congenitally corrected transposition: what should we do with all of these options supported by little evidence?

Despite the conceptually proper physiology consisting of independent in-series pulmonary and systemic circuits, the prognosis in patients with unoperated congenitally corrected transposition of the great arteries (ccTGA) is reserved, even in the absence of associated defects. This is attributable to several factors. Although reports have described unoperated patients with normal or near-normal systemic right ventricular (RV) function in their 60s and beyond (1,2), it is the exception rather than the rule. Faced with a systemic circulation, the morphologic RV fails in one third of patients with no associated lesions by the fifth decade of life, and in two thirds with prior surgery for concomitant defects by 45 years of age (3). When confronted with chronic pressure overload, the systemic RV invariably undergoes hypertrophic remodelling. Owing to its limited coronary reserve from the concordant predominantly single right coronary circulation, myocardial oxygen/supply mismatch can promote subendocardial ischemia, progressive fibrosis, and ultimately, overt heart failure (4-6). Second, the tricuspid valve, again part of the systemic circulation, frequently displays Ebsteinoid features with propensity for regurgitation. While the direction of the causal relationship between tricuspid insufficiency and RV dysfunction remains debated, RV failure often follows systemic atrioventricular (AV) regurgitation (7,8). Incompetence of the tricuspid valve correlates with excess mortality, with poorer outcomes following AV valve replacement when the pre-operative RV ejection fraction is ≤40% (9). In addition, the AV conduction system is displaced and susceptible to AV block (10,11). Longterm studies report a prevalence of complete AV block of 24–39% (3,12), with an annual incidence estimated to be approximately 2% per year (13). Pacemakers are, therefore, frequently indicated. In the absence of cardiac resynchronization therapy, pacing of the subpulmonary left ventricle can alter the ventricular depolarization pattern thereby precipitating systemic AV valve regurgitation and heart failure (14). This confluence of factors contributes to the risk for ventricular arrhythmias and sudden death (15).

Surgical strategy for aortic arch reconstruction after the Norwood procedure based on numerical flow analysis.

Inefficient aortic flow after the Norwood procedure is known to lead to the deterioration of ventricular function due to an increased cardiac workload. To prevent the progression of aortic arch obstruction, arch reconstruction concomitant with second-stage surgery is recommended. The aim of this study was to determine the indications for reconstruction based on numerical simulation and to reveal the morphology that affects the haemodynamic parameters. Fifteen patients who underwent the Norwood procedure or arch repair and Damus-Kaye-Stansel anastomosis were enrolled. The pressure gradient in aortic arch was 1.6 ± 3.9 mmHg (ranged from 0 to 12 mmHg) on catheter examination. Six patients who had prominent turbulent flow accompanied with a large flow energy loss index greater than 40 mW/m2 and high wall shear stress greater than 100 Pa underwent arch reconstruction. After arch reconstruction, the energy loss index significantly decreased from 88.5 ± 50.0 mW/m2 to 23.1 ± 10.4 mW/m2 (P = 0.026) and wall shear stress significantly decreased from 194.5 ± 87.4 Pa to 60.3 ± 40.5 Pa (P = 0.0062). There were 3 late deaths due to heart failure caused by progressive atrioventricular valve regurgitation during the follow-up period (60 months). The systemic ventricular function was preserved in the remaining patients without any pressure gradients in the arch. Determining the surgical strategy for arch reconstruction based on numerical flow analysis may effectively reduce the ventricular load even if no stenosis or pressure gradients are observed on catheter examination or echocardiography.

A vascular endothelial growth factor A genetic variant is associated with improved ventricular function and transplant-free survival after surgery for non-syndromic CHD.

We have previously shown that the minor alleles of vascular endothelial growth factor A (VEGFA) single-nucleotide polymorphism rs833069 and superoxide dismutase 2 (SOD2) single-nucleotide polymorphism rs2758331 are both associated with improved transplant-free survival after surgery for CHD in infants, but the underlying mechanisms are unknown. We hypothesised that one or both of these minor alleles are associated with better systemic ventricular function, resulting in improved survival. This study is a follow-up analysis of 422 non-syndromic CHD patients who underwent neonatal cardiac surgery with cardiopulmonary bypass. Echocardiographic reports were reviewed. Systemic ventricular function was subjectively categorised as normal, or as mildly, moderately, or severely depressed. The change in function was calculated as the change from the preoperative study to the last available study. Stepwise linear regression, adjusting for covariates, was performed for the outcome of change in ventricular function. Model comparison was performed using Akaike's information criterion. Only variables that improved the model prediction of change in systemic ventricular function were retained in the final model. Genetic and echocardiographic data were available for 335/422 subjects (79%). Of them, 33 (9.9%) developed worse systemic ventricular function during a mean follow-up period of 13.5 years. After covariate adjustment, the presence of the VEGFA minor allele was associated with preserved ventricular function (p=0.011). These data support the hypothesis that the mechanism by which the VEGFA single-nucleotide polymorphism rs833069 minor allele improves survival may be the preservation of ventricular function. Further studies are needed to validate this genotype-phenotype association and to determine whether this mechanism is related to increased vascular endothelial growth factor production.

Design for the sacubitril/valsartan (LCZ696) compared with enalapril study of pediatric patients with heart failure due to systemic left ventricle systolic dysfunction (PANORAMA-HF study)

Sacubitril/valsartan (LCZ696) is an angiotensin receptor neprilysin inhibitor approved for the treatment of adult heart failure (HF); however, the benefit of sacubitril/valsartan in pediatric HF patients is unknown. This global multi-center study will use an adaptive, seamless two-part design. Part 1 will assess the pharmacokinetics/pharmacodynamics of single ascending doses of sacubitril/valsartan in pediatric (1 month to <18 years) HF patients with systemic left ventricle and reduced left ventricular systolic function stratified into 3 age groups (Group 1: 6 to <18 years; Group 2: 1 to <6 years; Group 3: 1 month to <1 year). Part 2 is a 52-week, efficacy and safety study where 360 eligible patients will be randomized to sacubitril/valsartan or enalapril. A novel global rank primary endpoint derived by ranking patients (worst-to-best outcome) based on clinical events such as death, initiation of mechanical life support, listing for urgent heart transplant, worsening HF, measures of functional capacity (NYHA/Ross scores), and patient-reported HF symptoms will be used to assess efficacy. The PANORAMA-HF study, which will be the largest prospective pediatric HF trial conducted to date and the first to use a global rank primary endpoint, will determine whether sacubitril/valsartan is superior to enalapril for treatment of pediatric HF patients with reduced systemic left ventricular systolic function.

Study design and rationale for ELPIS: A phase I/IIb randomized pilot study of allogeneic human mesenchymal stem cell injection in patients with hypoplastic left heart syndrome

Despite advances in surgical technique and postoperative care, long-term survival of children born with hypoplastic left heart syndrome (HLHS) remains limited, with cardiac transplantation as the only alternative for patients with failing single ventricle circulations. Maintenance of systemic right ventricular function is crucial for long-term survival, and interventions that improve ventricular function and avoid or defer transplantation in patients with HLHS are urgently needed. We hypothesize that the young myocardium of the HLHS patient is responsive to the biological cues delivered by bone marrow-derived mesenchymal stem cells (MSCs) to improve and preserve right ventricle function. The ELPIS trial (Allogeneic Human MEsenchymal Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome: An Open Label Pilot Study) is a phase I/IIb trial designed to test whether MSC injection will be both safe and feasible by monitoring the first 10 HLHS patients for new major adverse cardiac events. If our toxicity stopping rule is not activated, we will proceed to the phase IIb component of our study where we will test our efficacy hypothesis that MSC injection improves cardiac function compared with surgery alone. Twenty patients will be enrolled in a randomized phase II trial with a uniform allocation to MSC injection versus standard surgical care (no injection). The 2 trial arms will be compared with respect to improvement of right ventricular function, tricuspid valve annulus size, and regurgitation determined by cardiac magnetic resonance and reduced mortality, morbidity, and need for transplantation. This study will establish the safety and feasibility of allogeneic mesenchymal stem cell injection in HLHS patients and provide important insights in the emerging field of stem cell-based therapy for congenital heart disease patients.

Effect of phosphodiesterase-5 inhibition with Tadalafil on SystEmic Right VEntricular size and function – A multi-center, double-blind, randomized, placebo-controlled clinical trial – SERVE trial - Rational and design

BackgroundPatients with a systemic right ventricle (RV) have a compromised late outcome caused by ventricular dysfunction. Standard medical heart failure therapy has not been shown to improve RV function and survival in these patients. Phosphodiesterase (PDE)-5 inhibition increases contractility in experimental models of RV hypertrophy, but not in the normal RV. In clinical practice, the effects of PDE-5 inhibition on systemic RV function and exercise capacity in adults with a systemic RV have not been tested. MethodsThe SERVE protocol is a double-blind, randomized placebo-controlled multicenter superiority trial to study the effect of PDE-5 inhibition with Tadalafil on RV volumes and function in patients with either D-transposition of the great arteries repaired with an atrial switch procedure or with congenitally corrected transposition of the great arteries. Tadalafil 20mg or placebo will be given over a study period of 3years. The primary endpoint is the change in mean end-systolic RV volumes from baseline to study end at 3years of follow-up (or at the time of permanent discontinuation of the randomized treatment if stopped before 3- years of follow-up), and will be measured by cardiovascular magnetic resonance imaging (CMR) or by cardiac computed tomography in patients with contraindications for CMR. Secondary endpoints are changes in RV ejection fraction, VO2max and NT-proBNP. ConclusionThe objective of this study is to assess the effect of PDE-5 inhibition with Tadalafil on RV size and function, exercise capacity and neurohumoral activation in adults with a systemic RV over a 3-year follow-up period.

Sudden cardiac death in adults with congenital heart disease: does QRS-complex fragmentation discriminate in structurally abnormal hearts?

Sudden cardiac death (SCD) causes a large portion of all mortality in adult congenital heart disease (ACHD) patients. However, identification of high-risk patients remains challenging. Fragmented QRS-complexes (fQRS) are a marker for SCD in patients with acquired heart disease but data in ACHD patients are lacking. We therefore aim to evaluate the prognostic value of fQRS for SCD in ACHD patients. From a multicentre cohort of 25790 ACHD patients, we included tachyarrhythmic SCD cases (n = 147), and controls (n = 266) matched by age, gender, congenital defect and (surgical) intervention. fQRS was defined as ≥1 discontinuous deflection in narrow QRS-complexes, and ≥2 in wide QRS-complexes (>120 ms), in two contiguous ECG leads. We calculated odds ratios (OR) using univariable and multivariable conditional logistic regression models correcting for impaired systemic ventricular function, heart failure and QRS duration >120 ms. ECGs of 147 SCD cases (65% male, median age of death 34 years) and of 266 controls were assessed. fQRS was present in 51% of cases and 34% of controls (OR 2.0, P = 0.003). In multivariable analysis, fQRS was independently associated with SCD (OR 1.9, P = 0.01). The most common diagnose of SCD cases was tetralogy of Fallot (ToF, 34 cases). In ToF, fQRS was present in 71% of cases vs. 43% of controls (OR for SCD 2.8, P = 0.03). fQRS was independently associated with SCD in ACHD patients in a cohort of SCD patients and matched controls. fQRS may therefore contribute to the decision when evaluating ACHD patients for primary prevention of SCD.

High sensitivity cardiac troponin T and systemic right ventricular function in adults with congenitally corrected transposition of the great arteries

BackgroundHigh sensitive troponin T (hsTnT), a marker of myocardial injury, appears to be a promising diagnostic tool in patients with congenital heart disease. However, little is known about its distribution among adults with systemic right ventricle (sRV). We aimed to assess the distribution of hsTnT concentrations in patients with congenitally corrected transposition of the great arteries (ccTGA) and to evaluate its relationship with sRV function and NT-proBNP. MethodsA cross-sectional study of adults with ccTGA was conducted. Patients underwent transthoracic echocardiography, hs-TnT and NTproBNP measurements. In the echocardiographic study, the sRV function was assessed qualitatively and quantitatively using fractional area change (FAC), TAPSE, myocardial performance index (MPI), systolic pulsed Doppler velocity (s′) and global longitudinal strain (GLS. ResultsFifty patients with ccTGA (20F/30M) and a mean age of 34.8±13.6years (range 18-63years) were included, with 27 of them (54%) having detectable hsTnT. Patients with detectable hsTnT were older and more often had NYHA class>I. Detectable hsTnT was associated with lower FAC (0.35 vs. 0.41, p<0.01) and GLS (−14.4% vs. -17.8%, p<0.01)) and higher MPI (0.67 vs. 0.48, p<0.01)). Hs-TnT correlated weekly with NT-proBNP (r=0.38; p<0.001). The area under the curve for the detection of sRV dysfunction (FAC<0.35) was higher for hs-TnT (0.839; CI 0.713-0.952) than for NT-proBNP (0.709; CI 0.545-0.873). ConclusionHsTnT was detectable in over half of the ccTGA population and was related to the sRV function. Compared to NTproBNP, hsTnT level seems to be superior biomarker in discriminating patients with sRV dysfunction.

Assessment of systemic right ventricular function in adult overweight and obese patients with congenitally corrected transposition of the great arteries.

In congenitally corrected transposition of the great arteries the right ventricle (RV) supports systemic circulation, and patients are prone to develop heart failure over time. Chronic volume overload secondary to obesity may contribute to premature dysfunction of the systemic RV. The aim of our study was to assess the systemic RV function in overweight/obese adult patients with congenitally corrected transposition of the great arteries. Transthoracic echocardiographic studies and laboratory testing (N-terminal pro-B-type natriuretic peptide [NT-proBNP] assessment) were performed in patients with congenitally corrected transposition, who were scheduled for a routine examination, and the body mass index was calculated for each patient. We studied 56 adults (31 men; mean age 33.9 years); 22 of whom were overweight (body mass index [BMI] of 25-29.9 kg/m²) or obese (BMI of 30 kg/m² or more), and 34 of whom were normal weight (BMI below 25 kg/m²). Age, gender, heart rate, and blood pressure were similar in both groups. The mean NT-proBNP levels were not significantly different. On echocardiography, the overweight/obese patients had a decreased systemic RV fractional area change (0.38) compared to normal weight patients (0.43); p = 0.02. Moreover, a significant reduction in the global longitudinal strain in the overweight/obese group was observed (-15.3% vs. -18.3%; p = 0.01). Overweight/obesity in adult patients with congenitally corrected transposition of the great arteries is associated with impaired systemic RV function.