Subclinical Cardiac Dysfunction in Childhood Cancer Survivors on 10-Years Follow-Up Correlates With Cumulative Anthracycline Dose and Is Best Detected by Cardiopulmonary Exercise Testing, Circulating Serum Biomarker, Speckle Tracking Echocardiography, and Tissue Doppler Imaging

Background: Survivors of childhood cancer are at risk for anthracycline- and/or radiotherapy-induced cardiotoxicity. Aims: The aim of this study was to assess clinical, laboratory, and imaging parameters of subclinical cardiovascular disease in childhood cancer survivors. Methods: Patients underwent cardiopulmonary exercise test (CPET), laboratory testing, transthoracic echocardiography (TTE) with tissue doppler imaging (TDI) and speckle tracking. A subset of patients also underwent cardiovascular magnetic resonance imaging (CMR). Findings were correlated to cumulative anthracycline and exposure to mediastinal irradiation during cancer treatment. In a subgroup analysis, TTE and CMR findings were compared to data from 40 gender- and age-matched patients with childhood onset hypertrophic cardiomyopathy (HCM). Results: Cardiac evaluation was performed in 79 patients (43 males) at 11.2 ± 4.5 years after cancer treatment. Oncologic diagnosis at a median age of 12.0 years was Hodgkin lymphoma in 20, sarcoma in 17, acute leukemia in 24, relapse leukemia in 10, and others in 8 patients. Cumulative anthracycline dose exceeded 300 mg/m2 in 28 patients. Twenty six patients also received mediastinal irradiation. Decreased peak respiratory oxygen uptake in % predicted on CPET, increased levels of N-terminal pro-brain natriuretic peptide (NTproBNP), increased global longitudinal strain on TTE speckle tracking, and diastolic dysfunction on TDI were the most prominent findings on detailed cardiology follow-up. In contrast to HCM patients, childhood cancer survivors did not show left ventricular hypertrophy (LVPWd z-score median 0.9 vs. 2.8, p < 0.001), hyperdynamic systolic function on TTE (Ejection fraction 62 ± 7 vs. 72 ± 12%, p = 0.001), or fibrotic myocardial changes on CMR (Late gadolinium positive 0/13 vs. 13/36, p = 0.001; extracellular volume fraction 22 ± 2 vs. 28 ± 3, p < 0.001) at time of follow-up. There was no correlation between chest radiation exposure and abnormal cardiac findings. Cumulative anthracycline dose was the only significant independent predictor on multivariate analysis for any cardiovascular abnormality on follow-up (p = 0.036). Conclusion: Increasing cumulative anthracycline dose during cancer treatment correlates with subclinical cardiac dysfunction in childhood cancer survivors best detected by elevated cardiac serum biomarkers, decreased exercise capacity on CPET, and abnormalities on echocardiographic speckle tracking and TDI

Reduced Handgrip Strength in Congenital Heart Disease With Regard to the Shunt Procedure in Infancy

Objective: In many patients with congenital heart disease (CHD) arterial blood flow to the arms is inhibited due to shunt surgery in infancy. This study investigates the handgrip strength of patients with CHD in regard to previous shunt procedures.Patients and Methods: Handgrip was evaluated in 424 patients with various CHD (189 female, age 28.1 ± 13.4 years) including 63 with shunt procedures in infancy; and 123 controls (51 female, 35.6 ± 14.2 years) using a Jamar dynamometer adjusted for hand size. The best of three repetitions was recorded for each side and the right-to-left hand ratio was calculated. The 63 shunted patients were grouped considering the side of the shunt: 14 right, 35 central and 14 left.Results: Patients with CHD, especially shunts, had significantly lower handgrip strength in the dominant hand than controls (controls: 43.2 ± 14.8 kg, CHD: 36.8 ± 14.8 kg, left shunt: 33.6 ± 14.6 kg, central shunt: 30.7 ± 15.2 kg and right shunt 27.8 ± 13.6 kg; p &lt; 0.001). In controls the right hand was 8.3% stronger, comparable to patients with either no shunt or central shunt (controls: 8.3 ± 13.2%; no shunt: 7.9 ± 15.3%; central shunt: 9.5 ± 18.1% p = 0.820). In patients with a left shunt the right hand was 22.5 ± 17.8% stronger than the left (p = 0.027 compared to central) while in those with a right shunt the right hand was 2.3 ± 18.3% weaker (p = 0.049 compared to central).Conclusions: Shunt procedures in infancy cause reduced handgrip strength in adulthood and diminished handgrip strength of the ipsilateral site

Oxygen Availability in Respiratory Muscles During Exercise in Children Following Fontan Operation

Introduction: As survival of previously considered as lethal congenital heart disease forms is the case in our days, issues regarding quality of life including sport and daily activities emerge. In patients with Fontan circulation, there is no pump to propel blood into the pulmonary arteries since the systemic veins are directly connected to the pulmonary arteries. The complex hemodynamics of Fontan circulation include atrial function, peripheral muscle pump, integrity of the atrioventricular valve, absence of restrictive, or obstructive pulmonary lung function. Therefore, thoracic mechanics are of particular importance within the complex hemodynamics of Fontan circulation.Methods: To understand the physiology of respiratory muscles, the aim of this study was to examine the matching of auxiliary respiratory muscle oxygen delivery and utilization during incremental exercise in young male Fontan patients (n = 22, age = 12.04 ± 2.51) and healthy Controls (n = 10, age = 14.90 ± 2.23). All subjects underwent a cardiopulmonary exercise test (CPET) to exhaustion whereas respiratory muscle oxygenation was measured non-invasively using a near-infrared spectrometer (NIRS).Results: CPET revealed significantly lower peak power output, oxygen uptake and breath activity in Fontan patients. The onset of respiratory muscle deoxygenation was significantly earlier. The matching of local muscle perfusion to oxygen demand was significantly worse in Fontans between 50 and 90% V.O2peak.Findings: The results indicate that (a) there is high strain on respiratory muscles during incremental cycling exercise and (b) auxiliary respiratory muscles are worse perfused in patients who underwent a Fontan procedure compared to healthy Controls. This might be indicative of a more general skeletal muscle strain and worse perfusion in Fontan patients rather than a localized-limited to thoracic muscles phenomenon

Impact of home monitoring program on interstage mortality after the Norwood procedure

ObjectiveWhile early outcome after the Norwood operation for hypoplastic left heart syndrome has improved, interstage mortality until bidirectional cavopulmonary shunt (BCPS) remains a concern. Our aim was to institute a home monitoring program to (HMP) decrease interstage mortality.MethodsAmong 264 patients who survived Norwood procedure and were discharged before BCPS, 80 patients were included in the HMP and compared to the remaining 184 patients regarding interstage mortality. In patients with HMP, events during the interstage period were evaluated.ResultsInterstage mortality was 8% (n = 21), and was significantly lower in patients with HMP (2.5%, n = 2), compared to those without (10.3%, n = 19, p = 0.031). Patients with interstage mortality had significantly lower birth weight (p &lt; 0.001) compared to those without. Lower birth weight (p &lt; 0.001), extra corporeal membrane oxygenation support (p = 0.002), and lack of HMP (p = 0.048) were risk factors for interstage mortality. Most frequent event during home monitoring was low saturation (&lt;70%) in 14 patients (18%), followed by infection in 6 (7.5%), stagnated weight gain in 5 (6.3%), hypoxic shock in 3 (3.8%) and arrhythmias in 2 (2.5%). An unexpected readmission was needed in 24 patients (30%). In those patients, age (p = 0.001) and weight at BCPS (p = 0.007) were significantly lower compared to those without readmission, but the survival after BCPS was comparable between the groups.ConclusionsInterstage HMP permits timely intervention and led to an important decrease in interstage mortality. One-third of the patients with home monitoring program needed re-admission and demonstrated the need for earlier stage 2 palliation

A study of factors related to the reorganization of municipal boundaries in Saskatchewan

The problems of municipal government in Saskatchewan have been varied in nature and often unwieldy in their scope. The roots of these problems have likewise originated, not in one particular spot, but rather in a number of conditions characteristic of the economy and the times in which the people have striven for sound government. Even the earliest settlers required an organization for government. Local roads, schools and other services had to be provided and the financing of such endeavors meant that the local government had to have the powers whereby it could levy taxes, borrow money and pass by-laws for the general welfare of the community. Thus we find municipal governments functioning even while the population was particularly sparse. Adjustments have been made in the organization of local government in Saskatchewan as time has progressed and as the changing requirements of these bodies have experienced the need for adjustment. It is felt by some at the present time that further changes in organization are required if the most effective government is to be provided. At the present time a proposal is being seriously considered which, if carried through, would bring about an enlargement of the areas contained in each rural municipality. In other words, a greater or lesser degree of agitation has developed for increasing the size of the unit served by each municipal council. It is the purpose of this investigation to enquire into the factors related to the reorganization of the municipalities into larger units. It is hoped that this may indicate some of the problems involved and serve in some measure to clarify the issues contained in the actions proposed

A restrictive ventilatory pattern is common in patients with univentricular heart after Fontan palliation and associated with a reduced exercise capacity and quality of life

AIM: The Fontan circulation is highly dependent on ventilation, improving pulmonary blood flow and cardiac output. A reduced ventilatory function is reported in these patients. The extent of this impairment and its relation to exercise capacity and quality of life is unknown and objective of this study. METHODS: This multicenter retrospective/cross-sectional study included 232 patients (140 females, age 25.6 ± 10.8 years) after Fontan palliation (19.8% atrioventricular connection; 20.3% atriopulmonary connection; 59.9% total cavopulmonary connection). Resting spirometry, cardiopulmonary exercise tests, and quality-of-life assessment (SF-36 questionnaire) were performed between 2003 and 2015. RESULTS: Overall, mean forced expiratory volume in one second (FEV1 ) was 74.7 ± 17.8%predicted (%pred). In 59.5% of the patients, FEV1 was 80%, suggestive of a restrictive ventilatory pattern. Reduced FEV1 was associated with a reduced peakVO2 of 67.0 ± 17.6%pred. (r = 0.43, P < .0001), even if analyzed together with possible confounding factors (sex, BMI, age, years after palliation, number of interventions, scoliosis, diaphragmatic paralysis). Synergistically to exercise capacity, FEV1 was associated to quality of life in terms of physical component summary (r = 0.30, P = .002), physical functioning (r = 0.25, P = .008), bodily pain (r = 0.22, P = .02), and general health (r = 0.16, P = .024). Lower FEV1 was associated with diaphragmatic paralysis (P = .001), scoliosis (P = .001), higher number of interventions (P = .002), and lower BMI (P = .01). No correlation was found to ventricular morphology, type of surgeries, or other perioperative/long-term complications. CONCLUSIONS: This study shows that the common restrictive ventilatory pattern in Fontan patients is associated with lower exercise capacity and quality of life. Risk factors are diaphragmatic paralysis, scoliosis, a high total number of interventions and low BMI

Peak Oxygen Uptake on Cardiopulmonary Exercise Test Is a Predictor for Severe Arrhythmic Events during Three-Year Follow-Up in Patients with Complex Congenital Heart Disease

Patients with congenital heart disease (CHD) are at increased risk for severe arrhythmia and sudden cardiac death (SCD). Although implantable cardioverter defibrillators (ICD) effectively prevent SCD, risk stratification for primary prophylaxis in patients with CHD remains challenging. Patients with complex CHD undergoing CPET were included in this single-center study. Univariable and backwards stepwise multivariable logistic regression models were used to identify variables associated with the endpoint of severe arrhythmic event during three years of follow-up. Cut-off values were established with receiver operating characteristic (ROC) curve analysis. Survival analysis was conducted via Kaplan&ndash;Meier plots. Severe Arrhythmia was documented in 97 of 1194 patients (8.1%/3 years). Independent risk factors for severe arrhythmia during follow-up were old age and a low peak oxygen uptake (V.O2peak) on multivariable analysis. Patients with more advanced age and with V.O2peak values of less than 24.9 mL/min/kg were at significantly increased risk for the occurrence of severe arrhythmias during follow-up. The combined analysis of both risk factors yielded an additional benefit for risk assessment. Age at CPET and V.O2peak predict the risk for severe arrhythmic events and should be considered for risk stratification of SCD in patients with complex CHD