NT-proBNP in systemic right ventricles: a new cutoff level for risk stratification?

INTRODUCTION AND OBJECTIVES: The role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the risk prediction of patients with systemic right ventricles (sRV) is not well defined. The aim of this study was to analyze the prognostic value of NT-proBNP in patients with an sRV. METHODS: The prognostic value of NT-proBNP was assessed in 98 patients from the SERVE trial. We used an adjusted Cox proportional hazards model, survival analysis, and c-statistics. The composite primary outcome was the occurrence of clinically relevant arrhythmia, heart failure, or death. Correlations between baseline NT-proBNP values and biventricular volumes and function were assessed by adjusted linear regression models. RESULTS: The median age [interquartile range] at baseline was 39 [32-48] years and 32% were women. The median NT-proBNP was 238 [137-429] ng/L. Baseline NT-proBNP concentrations were significantly higher among the 20 (20%) patients developing the combined primary outcome compared with those who did not (816 [194-1094] vs 205 [122-357]; P = .003). In patients with NT-proBNP concentrations > 75th percentile (> 429 ng/L), we found an exponential increase in the sex- and age-adjusted hazard ratio for the primary outcome. The prognostic value of NT-proBNP was comparable to right ventricular ejection fraction and peak oxygen uptake on exercise testing (c-statistic: 0.71, 0.72 and 0.71, respectively). CONCLUSIONS: In patients with sRVs, NT-proBNP concentrations correlate with sRV volumes and function and may serve as a simple tool for predicting adverse outcomes.

Prognostic Value and Determinants of High-Sensitivity Cardiac Troponin T in Patients With a Systemic Right Ventricle: Insights From the SERVE Trial.

BACKGROUND: The determinants and prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) among patients with a systemic right ventricle are largely unknown. METHODS AND RESULTS: Ninety-eight patients from the randomized controlled SERVE (Effect of Phosphodiesterase-5 Inhibition With Tadalafil on Systemic Right Ventricular Size and Function) trial were included. The correlation between baseline hs-cTnT concentrations and biventricular volumes and function quantified by cardiac magnetic resonance or cardiac multirow detector computed tomography was assessed by adjusted linear regression models. The prognostic value of hs-cTnT was assessed by adjusted Cox proportional hazards models, survival analysis, and concordance statistics. The primary outcome was time to the composite of clinically relevant arrhythmia, hospitalization for heart failure, or all-cause death. Median age was 39 (interquartile range, 32-48) years, and 32% were women. Median hs-cTnT concentration was 7 (interquartile range, 4-11) ng/L. Coefficients of determination for the relationship between hs-cTnT concentrations and right ventricular end-systolic volume index and right ventricular ejection fraction (RVEF) were +0.368 (P=0.046) and -0.381 (P=0.018), respectively. The sex- and age-adjusted hazard ratio for the primary outcome of hs-cTnT at 2 and 4 times the reference level (5 ng/L) were 2.89 (95% CI, 1.14-7.29) and 4.42 (95% CI, 1.21-16.15), respectively. The prognostic performance quantified by the concordance statistics for age- and sex-adjusted models based on hs-cTnT, right ventricular ejection fraction, and peak oxygen uptake predicted were comparable: 0.71% (95% CI, 0.61-0.82), 0.72% (95% CI, 0.59-0.84), and 0.71% (95% CI, 0.59-0.83), respectively. CONCLUSIONS: Hs-cTnT concentration was significantly correlated with right ventricular ejection fraction and right ventricular end-systolic volume index in patients with a systemic right ventricle. The prognostic accuracy of hs-cTnT was comparable to that of right ventricular ejection fraction and peak oxygen uptake predicted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03049540.

Paediatric and adolescent athletes in Switzerland: age-adapted proposals for pre-participation cardiovascular evaluation.

High-level sports competition is popular among Swiss youth. Even though preparticipation evaluation for competitive athletes is widespread, screening strategies for diseases responsible for sudden death during sport are highly variable. Hence, we sought to develop age-specific preparticipation cardiovascular evaluation (PPCE) proposals for Swiss paediatric and adolescent athletes (under 18 years of age). We recommend that all athletes practising in a squad with a training load of at least 6 hours per week should undergo PPCE based on medical history and physical examination from the age of 12 years on. Prior to 12 years, individual judgement of athletic performance is required. We suggest the inclusion of a standard 12-lead electrocardiogram (ECG) evaluation for all post-pubertal athletes (or older than 15 years) with analysis in accordance with the International Criteria for ECG Interpretation in Athletes. Echocardiography should not be a first-line screening tool but rather serve for the investigation of abnormalities detected by the above strategies. We recommend regular follow-up examinations, even for those having normal history, physical examination and ECG findings. Athletes with an abnormal history (including family history), physical examination and/or ECG should be further investigated and pathological findings discussed with a paediatric cardiologist. Importantly, the recommendations provided in this document are not intended for use among patients with congenital heart disease who require individualised care according to current guidelines.

Myocardial blood flow and cardiac sympathetic innervation in young adults late after arterial switch operation for transposition of the great arteries.

BACKGROUND: The arterial switch operation (ASO) for repair of transposition of the great arteries (TGA) requires transection of the great arterial trunks and re-implantation of the coronary arteries into the neoaortic root resulting in cardiac sympathetic denervation which may affect myocardial blood flow (MBF) regulation. The aims of the present study were to evaluate sympathetic (re-)innervation in young adults after ASO and its impact on MBF. METHODS: Twelve patients (age 22.5 ±â€¯2.6 years) after ASO for TGA in the neonatal period and ten healthy controls (age 22.0 ±â€¯1.7 years) were included. Positron emission tomography (PET) was used for measuring cardiac sympathetic innervation with [11C]meta-hydroxyephedrine (mHED) and MBF with [15O]H2O PET at rest, during adenosine stimulation, and during sympathetic stimulation with cold pressor test. Cold pressor-induced MBF response capacity was calculated as maximal global MBF over peak rate-pressure product multiplied by 10'000. RESULTS: Global [11C]mHED uptake was significantly lower in patients compared to controls (7.0 ±â€¯2.3 versus 11.8 ±â€¯2.1%/min, p < 0.001). Global MBF was lower in patients compared to controls at rest and during adenosine-induced hyperemia (0.66 ±â€¯0.08 versus 0.82 ±â€¯0.15 ml/min/g, p = 0.005; 2.23 ±â€¯1.19 versus 3.36 ±â€¯1.04 ml/min/g, p = 0.030, respectively). Interestingly, MBF during cold pressor test did not differ between patients and controls (0.99 ±â€¯0.20 versus 1.07 ±â€¯0.16 ml/min/g, p = 0.330). However, cold pressor-induced MBF response capacity was significantly lower for patients as compared to controls (1.09 ±â€¯0.35 versus 1.44 ±â€¯0.39 ml/g/10,000 mmHg, p = 0.040). CONCLUSIONS: With only partial sympathetic re-innervation of the coronary arteries, maximal dilator capacity of the coronary microvasculature and cold pressor-induced MBF response capacity remain substantially impaired in young adults after ASO compared to healthy controls.

The impact of trisomy 21 on treatment modalities and outcome in adults with congenital heart disease in Switzerland.

Trisomy 21 (T21) is associated in 40-45% of cases with heart defects, most commonly shunt lesions. These defects, if not repaired, can lead to irreversible shunt-induced pulmonary hypertension (i.e. Eisenmenger syndrome [ES]). In ES patients, intracardiac repair is no longer possible, but selective pulmonary vasodilators may increase exercise capacity and improve prognosis. This study aimed to estimate the prevalence of cardiac defects and ES in adult T21 patients and to assess the impact of T21 on treatment modalities and outcome in ES patients. A questionnaire was sent to 6906 Swiss physicians inviting them to indicate the number of adults with T21 under their care (survey report). We also analyzed all adults with ES (with and without T21) included in the Swiss Adult Congenital HEart disease Registry (SACHER) and studied the impact of T21 on the use of selective pulmonary vasodilators and survival. In the survey, 348 physicians cared for 695 adult T21 patients. Overall, 24% of T21 survey patients were known to have a cardiac defect, one in four with a defect had developed ES and 13% of those with ES were on specific pulmonary vasodilators. In SACHER, ES was present in 2% of adults with congenital heart disease and selective pulmonary vasodilators were used in 68% of ES patients with T21. In SACHER, survival during follow-up was worse with higher nt-proBNP levels (hazard ratio [HR] = 1.15 per 1000 units, 95% confidence interval [CI] = 1.02-1.29) and lower left ventricular ejection fraction (HR = 1.07 per percent decrease, 95% CI = 1.01-1.13). Age at inclusion and T21 did not affect survival. The prevalence of cardiac defects in adults with T21 in Switzerland is half the prevalence in children. T21 is over-represented among adults with ES. Raised awareness of the therapeutic options for T21 patients with ES is warranted.

Swiss Adult Congenital HEart disease Registry (SACHER) - rationale, design and first results.

BACKGROUND: In 2013, a prospective registry for adults with congenital heart disease (CHD) was established in Switzerland, providing detailed data on disease characteristics and outcomes: Swiss Adult Congenital HEart disease Registry (SACHER). Its aim is to improve the knowledge base of outcomes in adults with CHD. The registry design and baseline patient characteristics are reported. METHODS: All patients with structural congenital heart defects or hereditary aortopathies, followed-up at dedicated adult CHD clinics, are asked to participate in SACHER. Data of participants are pseudonymised and collected in an electronic, web-based, database (secuTrial®). Collected data include detailed diagnosis, type of repair procedures, previous complications and adverse outcomes during follow-up. RESULTS: From May 2014 to December 2016, 2836 patients (54% male, mean age 34 ± 14 years), with a wide variety of congenital heart lesions, have been enrolled into SACHER. Most prevalent were valve lesions (25%), followed by shunt lesions (22%), cyanotic and other complex congenital heart disease (16%), diseases affecting the right heart, i.e., tetralogy of Fallot or Ebstein anomaly (15%), and diseases of the left ventricular outflow tract (13%); 337 patients (12%) had concomitant congenital syndromes. The majority had undergone previous repair procedures (71%), 47% of those had one or more reinterventions. CONCLUSION: SACHER collects multicentre data on adults with CHD. Its structure enables prospective data analysis to assess detailed, lesion-specific outcomes with the aim to finally improve long-term outcomes.

Vagal reactivation after exercise and cardiac autonomic nervous activity in adult Fontan patients without pacemakers.

PURPOSE: Patients with Fontan circulation have reduced heart rate variability (HRV) in supine position. However, neither cardiac autonomic nervous activity (CANA) in response to orthostatic challenge nor vagal reactivation by means of heart rate (HR) recovery after cessation of exercise have previously been investigated in Fontan patients. The aim of this study was to compare HRV in supine and standing position, as well as HR recovery between Fontan patients and healthy controls. METHODS: Eight Fontan patients (4 male/4 female) without pacemakers and 12 healthy volunteers (5m/7f) with minimum age of 18years were recruited. HR was measured by Holter-electrocardiogram. HRV was measured in supine position and after orthostatic challenge. The power of the high frequency (HF: 0.15Hz-0.4Hz) and low frequency (LF: 0.04Hz-0.15Hz) bands was analysed by fast-Fourier transformation. HR recovery was determined at 30s and 60s after termination of a maximal exercise test. RESULTS: In both supine and standing position, total power, HF and LF power were reduced in Fontan patients compared to controls (by approximately a factor of 10) while there was no differences in LF/HF power ratio. Response to orthostatic challenge was blunted in absolute power but normal in relative power. HR recovery was not different between groups. CONCLUSION: Fontan patients have greatly reduced HRV, a blood-pressure dependent marker of CANA, but normal HR recovery, a blood pressure independent marker of vagal reactivation, suggesting that vagal activity may be normal, and only vascular capacitance reduced.

Cardiopulmonary adaptation to short-term high altitude exposure in adult Fontan patients.

OBJECTIVE: High altitude-related hypoxia induces pulmonary vasoconstriction. In Fontan patients without a contractile subpulmonary ventricle, an increase in pulmonary artery pressure is expected to decrease circulatory output and reduce exercise capacity. This study investigates the direct effects of short-term high altitude exposure on pulmonary blood flow (PBF) and exercise capacity in Fontan patients. METHODS: 16 adult Fontan patients (mean age 28±7 years, 56% female) and 14 matched controls underwent cardiopulmonary exercise testing with measurement of PBF with a gas rebreathing system at 540 m (low altitude) and at 3454 m (high altitude) within 12 weeks. RESULTS: PBF at rest and at exercise was higher in controls than in Fontan patients, both at low and high altitude. PBF increased twofold in Fontan patients and 2.8-fold in the control group during submaximal exercise, with no significant difference between low and high altitude (p=0.290). A reduction in peak oxygen uptake at high compared with low altitude was observed in Fontan patients (22.8±5.1 and 20.5±3.8 mL/min/kg, p<0.001) and the control group (35.0±7.4 and 29.1±6.5 mL/min/kg, p<0.001). The reduction in exercise capacity was less pronounced in Fontan patients compared with controls (9±12% vs 17±8%, p=0.005). No major adverse clinical event was observed. CONCLUSIONS: Short-term high altitude exposure has no negative impact on PBF and exercise capacity in Fontan patients when compared with controls, and was clinically well tolerated. TRIAL REGISTRATION NUMBER: NCT02237274: Results.

Fetal Diagnosis of Right Atrial Aneurysms.

Right atrial aneurysm is a rare condition of unknown etiology, characterized by marked dilatation of the right atrial free wall. We report 2 symptomatic cases following a fetal diagnosis.

Academic achievement and satisfaction in adolescents with CHD.

OBJECTIVES: To evaluate academic achievement and satisfaction in adolescents with CHD. Study design Questionnaires were sent to all adolescents, aged between 17 and 20 years with CHD, currently treated at our hospital (n=326) in order to assess the patients' education and satisfaction with their academic career. Results were compared with the official community statistics. RESULTS: A total of 207 patients completed the questionnaires (participation rate 63.5%), 113 boys and 94 girls; 50% had completed mandatory school at the highest, 37.3% at the middle, and 12.7% at the lowest educational level. The distribution in the general population was comparable: 57.6, 32.5, and 9.9%, respectively (p=0.8). Adolescents with severe CHD were less likely to attain a higher educational level than those with moderate or mild CHD (p=0.03 for school grades 7-9). None of the other examined medical or socio-demographic factors, such as socio-economic status, foreign language, severity of CHD, cyanosis, and open heart surgery, were found to be associated with lower educational attainment. After the mandatory 9 years of schooling, 21.4% (n=44) of the patients with CHD compared with 16.7% in the general population attended higher school levels heading towards university education (p=0.7). From the 165 patients who provided information on career satisfaction, 79% regarded their job or school situation as being their desired one without a difference for those with severe CHD. CONCLUSION: School education in Swiss adolescents with CHD is very similar to the normal population. In addition, the majority of adolescents are satisfied with their educational career. This fact may be due to the good educational support provided during schooling.

Interventional closure of RPA-to-LA communication in an oligosymptomatic neonate.

UNLABELLED: Direct communication between the right pulmonary artery (RPA) and the left atrium (LA) is a very rare cardiac malformation. Clinical presentation of RPA-to-LA communication depends on the size of the communication, the amount of right-to-left shunt, the patient's age, and pulmonary vascular resistance. Patients with small communications usually present oligosymptomatic and are diagnosed at an older age. A delay of diagnosis bears the risk of severe complications and needs to be prevented by proper work-up of oligosymptomatic neonates. Treatment of RPA-to-LA communications used to be performed by surgical closure, and the interventional approach has only been established as a less invasive alternative in recent years. CONCLUSION: Although patients with small RPA-to-LA communications usually present oligosymptomatic, early diagnosis and treatment is essential to prevent life-threatening complications.

The left heart after pulmonary valve replacement in adults late after tetralogy of Fallot repair.

BACKGROUND: Adverse ventricular-ventricular interactions have been recognized in those with repaired tetralogy of Fallot (TOF) and severe pulmonary regurgitation. OBJECTIVE: We aimed to examine the impact of pulmonary valve replacement (PVR) on the left heart late after TOF repair. METHODS AND RESULTS: Left ventricular (LV) volumes and ejection fractions (EF) were analyzed in adults with severe pulmonary regurgitation after TOF repair with cardiac magnetic resonance imaging (CMR) before and after PVR. Thirty-nine patients (median age 33[20-65] years) were reviewed. Post-PVR, LVEF improved significantly in the entire cohort (50 ± 9%→54 ± 7%, p<0.001) and in those with moderately impaired (defined as LVEF ≤ 45%) preoperative LVEF (38 ± 5%→47 ± 6%, p<0.0001), but was not statistically different in those with relatively preserved (defined as LVEF >45%) preoperative LVEF. By multivariate linear regression analysis to evaluate independent CMR predictors of improved LVEF post-PVR for the entire cohort, the only CMR variable to emerge was preoperative LVEF (p=0.012, regression coefficient -0.54, SE 0.13). Whereas PVR resulted in increased LV filling in patients with relatively preserved preoperative LVEF reflected by an increase in LV end-diastolic volumes (77 ± 10→82 ± 16 mL/m(2), p=0.05), LV end-systolic volumes decreased after PVR in patients with impaired preoperative LVEF (65 ± 12→54 ± 10 mL/m(2), p=0.001) but LV end-diastolic volumes were not significantly changed. CONCLUSION: When LVEF is decreased after TOF repair, PVR appears to have a salutary effect on postoperative LVEF, thereby supporting the concept of recovery of adverse right-left heart interactions. Mechanisms of left heart improvement post-PVR differ depending on degree of preoperative LV systolic dysfunction.

Diagnosis and management of common fetal arrhythmias.

Fetal arrhythmias are detected in at least 2% of unselected pregnancies during routine obstetrical scans. Most common are transient, brief episodes of a slow or fast heart rate or of an irregular heart rhythm. Less common are prolonged or persistent abnormalities such as supraventricular tachycardia and complete heart block which may lead to low cardiac output, fetal hydrops and demise. The objectives of this review are to update the reader on the diagnosis and management of the more common arrhythmias.

Angiotensin-converting enzyme inhibitors in pediatric patients with mitral valve regurgitation-case-control study and review of the literature.

OBJECTIVES: To investigate the effectiveness of chronic administration of angiotensin-converting enzyme inhibitors in pediatric patients with mitral valve regurgitation. DESIGN, SETTING, PATIENTS, INTERVENTIONS: This was a case-control study of all echocardiograms of patients with moderate-to-severe mitral valve regurgitation, who underwent chronic administration of angiotensin-converting enzyme inhibitors between January 1990 and December 2006 at a single center. OUTCOME MEASURES: Echocardiographic parameters (left ventricular end-diastolic diameter, left ventricular posterior wall diameter, interventricular septum diameter, left atrium to aortic root diameter ratio, grade of mitral valve regurgitation, shortening fraction) were analyzed before and during therapy with angiotensin-converting enzyme inhibitors in 12 patients and compared with 12 patients without medications after one month and one year. RESULTS: Twenty-four consecutive pediatric patients (median age of 7 years with a range 1 month-16 years) with moderate-to-severe mitral valve regurgitation were included. Data are given as standard deviation scores (z-scores) derived from body-surface-adjusted normal values. During angiotensin-converting enzyme inhibition left ventricular end-diastolic diameter decreased from mean z-score 2.04 to 1.66 (after 1 month) and to 1.73 (after 1 year), while left ventricular posterior wall diameter decreased from 0.25 to 0.12 (after 1 year), respectively. Shortening fraction, interventricular septum diameter, grade of mitral valve regurgitation, and left atrium to aortic root diameter ratio remained stable. CONCLUSIONS: In this case-control study of patients with moderate-to-severe mitral valve regurgitation effectiveness of angiotensin-converting enzyme inhibition on left ventricular dimensions and function after 1 month and 1 year is limited. Reviewing the literature, the lack of long-term follow-up studies with large patient cohorts and controversial study-results in adults require a prospective long-term multicenter follow-up study in pediatric patients.

Clinical recognition and treatment of atrial ectopic tachycardia in newborns.

QUESTIONS: Atrial ectopic tachycardia (AET) may be difficult to diagnose in neonates and treatment can be complex especially in case of severe heart failure. This study addresses the clinical recognition and drug therapy of AET in neonates. METHODS: Retrospective chart and database review of neonates diagnosed with AET between 1994 and 2002. RESULTS: AET was diagnosed in 19 neonates at a median age of 18 days (range 0-64). A paroxysmal AET pattern was seen in 10 and a permanent in 9 patients. Tachycardia in the foetal or neonatal period indicated an arrhythmia in 8 patients while 11 showed non-specific symptoms. Severely depressed ventricular dysfunction was observed in 2 patients necessitating cardiovascular resuscitation in 1. The mean maximum paroxysmal AET rate was 213 bpm (range 178-227). For permanent AET, the median mean heart rate was 169 bpm (153-185) and the mean maximum heart rate was 212 bpm (range 196-274). Antiarrhythmic class Ic and III drugs alone or as combination therapy controlled AET in all 18 treated neonates and ventricular dysfunctions resolved. Proarrhythmic drug side effects were seen in 1 patient under propafenone therapy. CONCLUSIONS: AET in neonates is frequently recognised as paroxysmal or permanent tachycardia. Symptoms are often non-specific even though neonates and infants may develop severe ventricular dysfunction. A high degree of awareness is mandatory for neonatologists, paediatricians and primary care physicians to recognise AET in neonates. Class Ic and III antiarrhythmic drugs are effective in the treatment of neonatal AET. Monitoring for proarrhythmic drug side effects is mandatory.