Failing Homeostasis of Quadriceps Muscle Energy- and pH Balance During Bicycling in a Young Patient With a Fontan Circulation

Aims: Patients with a congenital heart condition palliated with a Fontan circulation generally present with decreased exercise capacity due to impaired cardiopulmonary function. Recently, a study in patients with a Fontan circulation reported evidence for abnormal vascular endothelial function in legmuscle. We investigated if abnormal skeletal muscle hemodynamics during exercise play a role in the limited exercise tolerance of Fontan patients. If so, abnormalities in intramuscular energy metabolism would be expected both during exercise as well as during post-exercise metabolic recovery. Methods: In a young patient with a Fontan circulation and his healthy twin brother we studied the in vivo dynamics of energy-and pH-balance in quadriceps muscle during and after a maximal in-magnet bicycling exercise challenge using 31-phosphorus magnetic resonance spectroscopy. An unrelated age-matched boy was also included as independent control. Results: Quadriceps phosphocreatine (PCr) depletion during progressive exercise was more extensive in the Fontan patient than in both controls (95% vs. 80%, respectively). Importantly, it failed to reach an intermittent plateau phase observed in both controls. Quadriceps pH during exercise in the Fontan patient fell 0.3 units at low to moderate workloads, dropping to pH 6.6 at exhaustion. In both controls quadriceps acidification during exercise was absent but for the maximal workload in the twin brother (pH 6.8). Post-exercise, the rate of metabolic recovery in the Fontan patient and both controls was identical (time constant of PCr recovery 32 +/- 4, 31 +/- 2, and 28 +/- 4 s, respectively). Conclusion: Homeostasis of quadriceps energy- and pH-balance during a maximal exercise test failed in the Fontan patient in comparison to his healthy twin brother and an age-matched independent control. Post-exercise metabolic recovery was normal which does not support the contribution of significant endothelial dysfunction affecting adequate delivery of oxidative substrates to the muscle to the lower exercise capacity in this particular Fontan patient. These results suggest that mitochondrial ATP synthetic capacity of the quadriceps muscle was intact but cardiac output to the leg muscles during exercise was insufficient to meet the muscular demand for oxygen. Therefore, improving cardiac output remains the main therapeutic target to improve exercise capacity in patients with a Fontan circulation

N-terminal pro-brain natriuretic peptide serum levels reflect attrition of the Fontan circulation

Objective: N-terminal pro-brain natriuretic peptide has an established role in the diagnosis and prognosis of heart failure. In Fontan patients, this peptide is often increased, but its diagnostic value in this particular non-physiologic, univentricular circulation is unclear. We investigated whether N-terminal pro-brain natriuretic peptide represents ventricular function or other key variables in Fontan patients.Methods and results: Ninety-five consecutive Fontan patients ≥10 years old who attended the outpatient clinic of the Center for Congenital Heart Diseases in 2012-2013 were included. Time since Fontan completion was 16 ± 9 years. Median N-terminal pro-brain natriuretic peptide was 114 (61-264) ng/l and was higher than gender-and age-dependent normal values in 54% of the patients. Peptide Z-scores were higher in patients in NYHA class III/IV compared to those in class I/II, but did not correlate with ventricular function assessed by MRI and echocardiography, nor with peak exercise capacity. Instead, peptide Z-scores significantly correlated with follow-up duration after Fontan completion (p < 0.001), right ventricular morphology (p = 0.004), indexed ventricular mass (p = 0.001), and inferior caval vein diameter (p < 0.001) (adjusted R= 0.615).Conclusions: N-terminal pro-brain natriuretic peptide levels in Fontan patients correlate with functional class, but do not necessarily indicate ventricular dysfunction. Increased peptide levels were associated with a longer existence of the Fontan circulation, morphologic ventricular characteristics, and signs of increased systemic venous congestion. Since the latter are known to be key determinants of the performance of the Fontan circulation, these findings suggest increase in N-terminal pro-brain natriuretic peptide levels to indicate attrition of the Fontan circulation, independent of ventricular function

Cardiac Magnetic Resonance Derived Left Ventricular Eccentricity Index and Right Ventricular Mass Measurements Predict Outcome in Children with Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is associated with increased right ventricular (RV) afterload, affecting RV remodeling and RV performance, a major determinant of outcome in PAH-patients. In children with PAH, treatment strategy is guided by risk stratification where noninvasive prognosticators are highly needed. The prognostic value of RV characteristics derived by cardiac magnetic resonance (CMR) has been scarcely studied in pediatric PAH. We aimed to identify CMR-derived morphometric and functional RV characteristics prognostic for outcome in children with PAH. From the Dutch National cohort, thirty-eight children with either idiopathic/heritable PAH (IPAH/HPAH) or PAH associated with congenital heart disease (PAH-CHD), who underwent CMR, were included (median (interquartile range) [IQR] age 13.0 years (10.8–15.0), 66% females). Patients had severe PAH, characterized by their World Health Organization Functional Class, increased N-terminal pro-B-type natriuretic peptide and high pulmonary arterial pressure and pulmonary vascular resistance index at time of CMR. RV-ejection fraction (RVEF), indexed RV-mass (RVMi), the ratio between RV and LV mass (RVM/LVM-ratio) and left ventricular eccentricity index (LVEI) all correlated with transplant-free survival from time of CMR. These correlations could not be confirmed in the PAH-CHD group. This study shows that CMR-derived measures reflecting RV function and remodeling (LVEI, RVMi, RVM/LVM-ratio, RVEF) predict transplant-free survival in children with IPAH/HPAH and may be included in risk stratification scores in pediatric PAH.</p

Off-pump hepatic to azygos connection via thoracotomy for relief of fistulas after a Kawashima procedure:Ten-year results

Objectives: An almost universal incidence of developing pulmonary arteriovenous fistulas after the Kawashima operation has been reported. Exclusion of the hepatic venous flow from the pulmonary circulation causes the development of these malformations. Redirection of hepatic venous flow to the pulmonary circulation mostly leads to the regression of the arteriovenous fistulas.Methods: We analyzed 11 patients with arteriovenous fistulas that developed after the Kawashima operation. The hepatic-to-azygos shunts were performed with an off-pump technique through a lateral thoracotomy in all but one. Operative and postoperative data were retrospectively collected.Results: No intraoperative complications occurred, and no patient died in the hospital. Up to 10-year follow-up showed a significant postoperative improvement of patients' oxygen saturation and New York Heart Association class. Apart from 2 re-thoracotomies for bleeding in 1 patient, no complications occurred and no patient died during follow-up. Two other patients underwent reoperation for an undiagnosed additional hepatic vein. The improvement of patients' oxygen saturation and New York Heart Association class persisted during the follow-up period.Conclusions: The surgical connection can be performed safely with an off-pump technique that avoids the risks related to extracorporeal circulation and circulatory arrest. The results at 10 years follow-up confirmed the efficacy and safety of the surgical technique described.</p

Serial cardiovascular magnetic resonance feature tracking indicates early worsening of cardiac function in Fontan patients

Background: In Fontan patients, attrition of ventricular function is well recognized, but early detection of ventricular dysfunction is difficult. The aim of this study is to longitudinally assess ventricular strain in Fontan patients using a new method for cardiac magnetic resonance (CMR) feature tracking, and to investigate the relationship between ventricular strain and cardiac systolic function. Methods and results: In this prospective, standardized follow-up study in 51 Fontan patients, age ≥ 10 years, CMR and concomitant clinical assessment was done at the start of the study and after 2 years. CMR feature tracking was done combining the dominant and hypoplastic ventricles. Global longitudinal strain (GLS) (−17.3% versus −15.9%, P = 0.041) and global circumferential strain (GCS) (−17.7 versus −16.1, P = 0.047) decreased over 2 years' time. Ejection fraction (EF) (57%), cardiac index (CI) (2.7 l/min/m2) and NYHA functional class (97% in class I/II) were preserved. The strain values of the combined dominant and hypoplastic ventricles were significantly worse compared to those of the dominant ventricle only (GLS −16.8 (−19.5 to −14.0) versus −18.8 (−21.3 to −15.3) respectively, P = 0.001, GCS −18.3 (−22.1 to −14.8) versus −22.5 (−26.3 to −19.4) respectively, P < 0.001). Conclusions: This study showed a decrease in cardiac strain over 2 years in Fontan patients without clinical signs of Fontan failure, where EF, CI and clinical status were still preserved. Cardiac strain might be a sensitive early indicator of systolic ventricular decline. Furthermore, combined strain of the hypoplastic and dominant ventricles seems a more accurate representation of cardiac strain in functionally univentricular hearts

GDF-15 (Growth Differentiation Factor 15) Is Associated With Hospitalization and Mortality in Patients With a Fontan Circulation

Background We investigated serial serum levels of GDF-15 (growth differentiation factor 15) in Fontan patients and their relation to outcome. Methods and Results In this single-center prospective study of consecutive Fontan patients, serial serum GDF-15 measurement and clinical assessment was done at baseline (n=81) and after 2 years (n=51). The association between GDF-15 and the combined end point of all-cause mortality, heart transplant listing, and Fontan-related hospitalization was investigated. Median age at baseline was 21 years (interquartile range: 15-28 years). Median GDF-15 serum levels at baseline were 552 pg/mL (interquartile range: 453-729 pg/mL). GDF-15 serum levels correlated positively with age, age at Fontan initiation, New York Heart Association class, and serum levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and ɣGT (γ-glutamyltransferase) and negatively with exercise capacity. During a median follow-up of 4.8 years (interquartile range: 3.3-5.5 years), the combined end point occurred in 30 patients (37%). Multivariate Cox regression showed that patients with the highest baseline GDF-15 (n=20, defined as the upper quartile) had a higher risk of hospitalization or death than the lowest 3 quartiles (hazard ratio [HR], 2.76; 95% CI, 1.27-6.00; P=0.011). After 2 years of follow-up, patients in whom serum level of GDF-15 increased to >70 pg/mL (n=13) had a higher risk of hospitalization or death than the lowest 3 quartiles (HR, 2.69; 95% CI, 1.03-6.99; P=0.043). Conclusions In Fontan patients, elevated serum levels of GDF-15 are associated with worse functional status and predict Fontan-related events. Furthermore, serial measurements showed that an increase in GDF-15 serum level was associated with increased risk for adverse outcome

CT-Derived Pulmonary Artery Diameters to Preselect for Echocardiography in COPD Patients Eligible for Bronchoscopic Treatments

Background: Currently, patients with COPD who are evaluated for bronchoscopic treatments are routinely screened for pulmonary hypertension (PH) and systolic left ventricle dysfunction by echocardiography. Objectives: We evaluated the prevalence of PH and systolic left ventricle dysfunction in this patient group and investigated if the previously proposed CT-derived pulmonary artery to aorta (PA:A) ratio >1 and PA diameter measurements can be used as alternative screening tools for PH. Methods: Two hundred fifty-five patients were included in this retrospective analysis (FEV1 25%pred, RV 237%pred). All patients received transthoracic echocardiography and chest CT scans on which diameters of the aorta and pulmonary artery were measured at the bifurcation and proximal to the bifurcation. Results: Following echocardiography, 3 patients (1.2%) had PH and 1 (0.4%) had systolic left ventricle dysfunction. Using a PA:A ratio >1, only 10.3% of the patients with a right ventricular systolic pressure (RVSP) >= 35 mm Hg were detected and none of the patients with an RVSP >50 mm Hg were detected. Patients with an RVSP >= 35 mm Hg had significantly higher PA diameters (29.5 vs. 27.5 mm; p = 0.02) but no significantly different PA:A ratios. All patients with an RVSP >50 mm Hg had PA diameters >30 mm. Conclusions: The prevalence of PH and systolic left ventricle dysfunction is low in this preselected cohort of patients with severe COPD. In this population, a PA:A ratio >1 is not a useful cardiac screening tool for PH. A PA diameter >30 mm could substitute for routinely performed echocardiography in the screening for PH in this patient group

The role of the combination of bone and fall related risk factors on short-term subsequent fracture risk and mortality

BACKGROUND: We analysed whether a combination of bone- and fall-related risk factors (RFs) in addition to a recent non-vertebral fracture (NVF) contributed to subsequent NVF risk and mortality during 2-years in patients who were offered fall and fracture prevention according to Dutch fracture- and fall-prevention guidelines. METHODS: 834 consecutive patients aged ≥50 years with a recent NVF who were included. We compared subgroups of patients according to the presence of bone RFs and/or fall RFs (group 1: only bone RFs; group 2: combination of bone and fall RFs; group 3: only fall RFs; group 4: no additional RFs). Univariable and multivariable Cox regression analyses were performed adjusted for age, sex and baseline fracture location (major or minor). RESULTS: 57 (6.8%) had a subsequent NVF and 29 (3.5%) died within 2-years. Univariable Cox regression analysis showed that patients with the combination of bone and fall RFs had a 99% higher risk in subsequent fracture risk compared to all others (Hazard Ratio (HR) 1.99; 95% Confidence Interval (CI) 1.18-3.36) Multivariable analyses this was borderline not significant (HR 1.70; 95% CI: 0.99-2.93). No significant differences in mortality were found between the groups. CONCLUSION: Evaluation of fall RFs contributes to identifying patients with bone RFs at highest immediate risk of subsequent NVF in spite of guideline-based treatment. It should be further studied whether earlier and immediate prevention following a NVF can decrease fracture risk in patients with a combination of bone and fall RFs

Implant Failure:STRATOS System for Pectus Repair

Background. Three European centers have recently reported dramatic failures of the STRATOS titanium system, approved in Europe and the United States since 2007 and meant for pectus repair, without detailed exploration of its causes. Methods. Failed implants (fractures or loosened crimp connectors) were surgically explanted from 12 patients and biopsies taken from surrounding discolored tissue. Detailed failure analysis was performed to find the cause of failures. Inductively coupled mass spectroscopy, scanning electron microscopy, and energy dispersive radiograph spectroscopy was used to determine titanium and to visualize titanium wear debris in histologic sections. Results. Implants failed in all patients by fracture of connecting bar, fracture of lateral bar at reduced cross-section, loosening of crimp connector, or different combinations of these. All fracture surfaces were clean and smooth without any signs of plastic deformation. Failure already started at 10 months after implantation and continued for 2.5 years. Biopsy of discolored tissue around the failures showed 0.4 mg to 105 mg titanium per gram tissue, and close observation showed titanium wear debris. Conclusions. Combined tensile, compressive, bending, and torsional loading on the implant during each breathing cycle caused loosening and fatigue fractures, which led to failure. Excessive rubbing at the fracture and loosening site caused the release of large amounts of titanium in the surrounding tissue, which may lead to metallosis. Long and sharp pieces of failed implant in the cardiothoracic region is a grave danger to vital organs. All patients should be closely followed, and in our opinion, all implants should be removed. Serious reconsideration for clinical use of this implant is necessary. (C) 2017 by The Society of Thoracic Surgeon