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.

Prognostic value of right ventricular dyssynchrony in adults with repaired tetralogy of Fallot.

OBJECTIVE: Residual sequelae after surgical repair of tetralogy of Fallot (rTOF) affect clinical outcome. We investigated the prognostic impact of right ventricular (RV) dyssynchrony in adults with rTOF years after the surgical repair. METHODS: Patients from the Swiss Adult Congenital HEart disease Registry were included. NT-proBNP levels, echocardiography, exercise testing and MRI data were collected. An offline strain analysis to quantify RV-ventricular and interventricular dyssynchrony was performed. The standard deviation of the time-to-peak shortening (TTP) of six RV segments defined the RV Dyssynchrony Index (RVDI). Maximal difference of TTP between RV and left ventricular segments defined the interventricular shortening delay (IVSD). Predictors of a composite adverse event (arrhythmias, hospitalisation for heart failure and death) were identified by multivariate Cox regression analysis. Their median values were used to create a risk score. RESULTS: Out of 285 included patients (mean age 34±14 years), 33 patients (12%) experienced an adverse event during a mean follow-up of 48±21 months. No correlation was found between RVDI, IVSD and clinical events. NT-proBNP, right atrial area and peak heart rate were independent predictors of outcomes. After 4 years-follow-up, no adverse events occurred in patients at low risk (score=0 points), while an adverse event occurred in 62% of patients at high risk (score=3 points, p<0.001). CONCLUSION: In our cohort of adults with rTOF, surrogates of RV dyssynchrony did not correlate with outcomes. A multimodality approach was effective in predicting the risk for adverse events.

Impact of pulmonary valve replacement on ventricular function and cardiac events in patients with tetralogy of Fallot. A retrospective cohort study.

INTRODUCTION AND OBJECTIVES: Our aim was to assess the impact of prosthetic pulmonary valve replacement (PVR) in patients with repaired tetralogy of Fallot (rTOF) on changes in biventricular volumes and function and on adverse cardiac events. METHODS: Adults with rTOF were identified from the SACHER-registry. Data from serial cardiac magnetic resonance imaging, echocardiography, exercise capacity and n-terminal pro b-type natriuretic peptide (NT-proBNP) were collected. The primary endpoint was right ventricular ejection fraction (RVEF) as measured by cardiac magnetic resonance. Secondary endpoints were biventricular volumes, left ventricular ejection fraction, exercise capacity and NT-proBNP levels, and time to adverse cardiac outcomes (atrial and ventricular arrhythmia, endocarditis). Associations between previous PVR and longitudinal changes in functional outcomes and time to adverse cardiac outcomes were analyzed using linear mixed-effects models and Cox proportional hazards models, respectively. RESULTS: A total of 308 patients (153 with and 155 without PVR) with 887 study visits were analyzed. Previous PVR was not significantly associated with changes in RVEF (CE, -1.33; 95%CI, -5.87 to 3.21; P=.566). Previous PVR was associated with lower right ventricular end-diastolic volume but had no significant effect on left ventricular ejection fraction, exercise capacity, or NT-proBNP-levels. Previous PVR was associated with an increased hazard of atrial arrhythmias (HR, 2.09; 95%CI, 1.17-3.72; P=.012) and infective endocarditis (HR, 12.72; 95%CI, 4.69-34.49; P<.0001) but not with an increased hazard of sustained ventricular arrhythmias (HR, 0.64; 95%CI, 0.18-2.27; P=.490). CONCLUSIONS: Previous PVR was not significantly associated with changes in RVEF but was associated with an increased risk of atrial arrhythmias and infective endocarditis.

Effect of phosphodiesterase-5 inhibition on SystEmic Right VEntricular size and function. A multicentre, double-blind, randomized, placebo-controlled trial: SERVE.

AIMS: In adults with congenital heart disease and systemic right ventricles, progressive right ventricular systolic dysfunction is common and is associated with adverse outcomes. Our aim was to assess the impact of the phosphodiesterase-5-inhibitor tadalafil on right ventricular systolic function. METHODS AND RESULTS: This was a double-blind, randomized, placebo-controlled, multicentre superiority trial (NCT03049540) involving 100 adults with systemic right ventricles (33 women, mean age: 40.7 ± 10.7 years), comparing tadalafil 20 mg once daily versus placebo (1:1 ratio). The primary endpoint was the change in right ventricular end-systolic volume after 3 years of therapy. Secondary endpoints were changes in right ventricular ejection fraction, exercise capacity and N-terminal pro-B-type natriuretic peptide concentration. Primary endpoint assessment by intention to treat analysis at 3 years of follow-up was possible in 83 patients (42 patients in the tadalafil group and 41 patients in the placebo group). No significant changes over time in right ventricular end-systolic volumes were observed in the tadalafil and the placebo group, and no significant differences between treatment groups (3.4 ml, 95% confidence interval -4.3 to 11.0, p = 0.39). No significant changes over time were observed for the pre-specified secondary endpoints for the entire study population, without differences between the tadalafil and the placebo group. CONCLUSIONS: In this trial in adults with systemic right ventricles, right ventricular systolic function, exercise capacity and neuro-hormonal activation remained stable over a 3-year follow-up period. No significant treatment effect of tadalafil was observed. Further research is needed to find effective treatment for improvement of ventricular function in adults with systemic right ventricles.

High Variability of Right Ventricular Volumes and Function in Adults with Severe Pulmonary Regurgitation Late After Tetralogy of Fallot Repair.

Our aim was to assess changes of right ventricular end-diastolic volumes (RVEDVi) and right ventricular ejection fraction (RVEF) in asymptomatic adults with repaired tetralogy of Fallot, with native right ventricular outflow tract and severe pulmonary regurgitation by serial cardiac magnetic resonance imaging (CMR). The study included 23 asymptomatic adults who underwent ≥3 CMR studies (total of 88 CMR studies). We compared changes in RVEDVi and RVEF between first and last study (median follow-up: 8.8 years, interquartile range: 6.3 to 13.1 years) and between all study pairs. Variability of measurements between study pairs (65 consecutive and 139 nonconsecutive CMR study pairs) were assessed using Bland-Altman analysis and intraclass correlation coefficients. On average, there were no significant changes of RVEDVi or RVEF over the study period (change in RVEDVi: +0.4 ± 17.8 ml/m2, change in RVEF: -1.0 ± 5.5%). Assessment of variability of measurements between study pairs demonstrated no systematic change in RVEDVi and RVEF between study pairs with limits of agreement within the range of previously published studies (RVEDVi -29.1 to +27.2 ml/m2; RVEF -11.5% to 10.2%). High intraclass correlation coefficients for RVEDVi (0.943, 95% CI 0.906 to 0.965, p <0.001) and RVEF (0.815, 95% CI 0.697 to 0.887, p <0.0001) indicate high reliability of reported measurements. In conclusion, in asymptomatic adults with repaired tetralogy of Fallot with native right ventricular outflow tracts and severe pulmonary regurgitation, CMR measurements of RV volumes and RVEF remain stable during follow-up with variability between CMR studies in individual patients, as expected for interobserver and interstudy variability. Measurements derived from a single CMR study or changes occurring between 2 CMR studies should be used with caution for clinical decision-making.

Multimodality Imaging for Evaluation of Bicaval Valved Stent Implantation in Severe Tricuspid Regurgitation.

Preprocedural planning and postprocedural evaluation after transcatheter treatment of severe tricuspid regurgitation remain challenging and require further research and standardization. We illustrate the use of multimodality imaging techniques in 3 patients undergoing implantation of a novel custom-made bicaval valved stent for symptomatic treatment of severe tricuspid regurgitation. (Level of Difficulty: Advanced.).

Cardiovascular MRI Compared to Echocardiography to Identify Cardioaortic Sources of Ischemic Stroke: A Systematic Review and Meta-Analysis.

Background: To compare the diagnostic yield of echocardiography and cardiovascular MRI (CMR) to detect structural sources of embolism, in patients with ischemic stroke with a secondary analysis of non-stroke populations. Methods and Results: We searched MEDLINE/Embase (from 01.01.2000 to 24.04.2021) for studies including CMR to assess prespecified sources of embolism. Comparison included transthoracic and/or transesophageal echocardiography. Two authors independently screened studies, extracted data and assessed bias using the QUADAS-2 tool. Estimates of diagnostic yield were reported and pooled. Twenty-seven studies with 2,525 patients were included in a study-level analysis. Most studies had moderate to high risk of bias. Persistent foramen ovale, complex aortic plaques, left ventricular and left atrial thrombus were the most common pathologies. There was no difference in the yield of left ventricular thrombus detection between both modalities for stroke populations (4 studies), but an increased yield of CMR in non-stroke populations (28.1 vs. 16.0%, P < 0.001, 10 studies). The diagnostic yield in stroke patients for detection of persistent foramen ovale was lower in CMR compared to transoesophageal echocardiography (29.3 vs. 53.7%, P < 0.001, 5 studies). For both echocardiography and CMR the clinical impact of the management consequences derived from many of the diagnostic findings remained undetermined in the identified studies. Conclusions: Echocardiography and CMR seem to have similar diagnostic yield for most cardioaortic sources of embolism except persistent foramen ovale and left ventricular thrombus. Randomized controlled diagnostic trials are necessary to understand the impact on the management and potential clinical benefits of the assessment of structural cardioaortic stroke sources. Registration: PROSPERO: CRD42020158787.

Subject-specific simulation for non-invasive assessment of aortic coarctation: Towards a translational approach.

We present a multi-scale CFD-based study conducted in a cohort of 11 patients with coarctation of the aorta (CoA). The study explores the potential for implementation of a workflow using non-invasive routinely collected medical imaging data and clinical measurements to provide a more detailed insight into local aortic haemodynamics in order to support clinical decision making. Our approach is multi-scale, using a reduced-order model (1D/0D) and an optimization process for the personalization of patient-specific boundary conditions and aortic vessel wall parameters from non-invasive measurements, to inform a more complex model (3D/0D) representing 3D aortic patient-specific anatomy. The reliability of the modelling approach is investigated by comparing 3D/0D model pressure drop estimation with measured peak gradients recorded during diagnostic cardiac catheterization and 2D PC-MRI flow rate measurements in the descending aorta. The current study demonstrated that the proposed approach requires low levels of user interaction, making it suitable for the clinical setting. The agreement between computed blood pressure drop and catheter measurements is 10  ±  8 mmHg at the coarctation site. The comparison between CFD derived and catheter measured pressure gradients indicated that the model has to be improved, suggesting the use of time varying pressure waveforms to further optimize the tuning process and modelling assumptions.

Cardiac Implantable Electronic Device-Related Infection Due to Granulicatella adiacens.

Cardiac implantable electronic device-related infection is clinically challenging. Curative treatment commonly includes system removal. A case caused by Granulicatella adiacens occurred in a 32-year-old woman. Clinical course, literature review, and biofilm investigations enabled successful antibiotic management without system removal.

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.

Elbasvir/Grazoprevir, an Alternative in Antiviral Hepatitis C Therapy in Patients under Amiodarone Treatment.

A sofosbuvir/ledipasvir combination is part of a first-line treatment of hepatitis C. However, in patients concurrently treated with amiodarone, cardiac side effects have been described, resulting in an official warning in 2015 by the American Food and Drug Administration and the European Medicines Agency when combining those substances. This deprived numerous hepatitis C patients with concurrent cardiovascular problems of receiving this highly effective treatment. Here we present a treatment alternative with an elbasvir/grazoprevir regimen, based on our successful treatment of a patient under concurrent amiodarone therapy. Our observations indicate that patients treated with amiodarone can finally benefit from effective antiviral therapy.

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.

Challenges of congenital heart disease in grown-up patients.

Nowadays, more than 90% of all children born with congenital heart disease (CHD) reach adult life. Although initially considered to be cured, the majority of them continue to need specialised follow-up because they require re-do interventions or are at increased risk of cardiovascular complications and premature death. Arrhythmias are the most common cause of unscheduled hospital visits for grown-up CHD (GUCH) patients, accounting for one third of emergency admissions in these patients. Some GUCH patients are also at increased risk for sudden cardiac death. The principles of arrhythmia management and the prevention of sudden cardiac death in GUCH patients are similar to those used in adults with acquired heart disease, but are not evidence based. Decompensated heart failure is the other leading cause of death. Conventional medical heart-failure therapy for left ventricular dysfunction is not effective in GUCH patients at highest risk of heart failure, i.e., those with right or single ventricular failure. Careful haemodynamic assessment and structural interventions are the first step to consider in GUCH patients presenting with heart failure symptoms. Adults with moderate or complex CHD and regular follow-up in specialised GUCH centres have a survival benefit compared with patients without such follow-up. Cardiac surgery in GUCH patients should be performed by surgeons trained in treatment of CHD, i.e., surgeons also operating on paediatric patients. A structured transition programme with a defined transfer of care from the paediatric to the adult care environment is important to avoid lapses of care in today's adolescents with CHD. For GUCH patients with an intervention performed decades ago and no specific cardiac follow-up in later life, referral to a specialised GUCH centre is recommended and may save lives.

Gender-related differences in self-reported dental care in adults with congenital heart disease at increased risk of infective endocarditis.

OBJECTIVE: Adults with congenital heart disease (CHD) are at increased risk of infective endocarditis (IE). Women with CHD have a lower IE risk, potentially due to gender-related differences in dental care. We aimed to assess self-reported dental hygiene measures in adults with CHD, and to identify factors associated with good oral hygiene. METHODS AND RESULTS: Descriptive study includes 187 adults with CHD at increased risk of IE. The patients' IE knowledge was assessed using an adapted version of the Leuven Knowledge Questionnaire for CHD. Their mean age was 34.9±14.9 years, 73 of them (39%) were women, 91 (49%) were at high risk for IE, including 66 (35%) with a prosthetic valve, 14 (7%) with a history of IE and 11 (6%) with cyanotic CHD or residual shunts/valvular regurgitation in the proximity of prosthetic material. The self-defined IE knowledge score did not differ between men and women (21.6±10.0 vs 23.4±10.0; p=0.225). 126 patients (67%) reported to have a good oral hygiene. Female gender (OR 2.4, 95% CI 1.1 to 4.4), and a higher IE knowledge score (OR 1.2, 95% CI 1.1 to 1.5, per 5 points) were the variables independently associated with good oral hygiene. CONCLUSIONS: In adults with CHD, patients with a higher IE knowledge score and women are more likely to practise dental care as recommended. Gender differences in oral hygiene practise may explain the observed lower female IE incidence rate. Efforts to improve patients' knowledge on IE are encouraged.

Left ventricular outflow tract obstruction and its impact on systolic ventricular function and exercise capacity in adults with a subaortic right ventricle.

BACKGROUND: In biventricular hearts the filling and contractility of one ventricle affects the performance of the other. In this study, we compared right ventricular systolic function and exercise capacity in patients with a subaortic right ventricle (RV) in relation to the presence of a left ventricular outflow tract obstruction (LVOTO). METHODS: Retrospective chart review of adults with congenitally corrected transposition of the great arteries (ccTGA) or with a previous atrial switch procedure for complete TGA (D-TGA). A LVOTO was defined by a peak instantaneous systolic gradient>20mmHg. Right and left ventricular ejection fraction (EF) were measured by cardiac magnetic resonance imaging (CMR), and exercise capacity as the predicted peak oxygen consumption (peak VO2) on a cycle ergometer. RESULTS: We identified 79 clinically stable adults (age 33±10years, 70% male). Nine patients (11%) had cc-TGA and 70 patients had (89%) D-TGA. Thirteen patients (16%) had a LVOTO with a mean peak instantaneous systolic gradient of 43±22mmHg. Patients with a LVOTO had higher left (68±7% vs. 60±9%, p=0.01) and right ventricular EF (52±8 vs. 46±9%, p=0.05) by CMR compared to patients without LVOTO. In a multivariate regression analysis with left ventricular EF and LVOTO as predictors, only left ventricular EF was independently associated with right ventricular EF (correlation coefficient 0.41, p<0.01). The presence of a LVOTO was not associated with improved exercise capacity. CONCLUSIONS: In adults with a subaortic RV, a pressure loaded subpulmonary left ventricle has a beneficial effect on systemic right ventricular EF.

Failing Systemic Right Ventricles With Persistent Pulmonary Hypertension: Candidates for Ventricular Assist Devices as Destination Therapy?

Dysfunction of the systemic right ventricle is common after the atrial switch procedure for transposition of the great arteries. Cardiac transplantation remains the only long-term solution in terminal systemic right ventricular (RV) failure, but concomitant pulmonary hypertension (PHT) may preclude it. The increasing number of such patients, together with the concerns related to combined heart-lung transplantation (HLTx), urge us to consider other therapeutic options.

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.