[Exercise Training in Patients with Pulmonary Hypertension: A Systematic Review and Meta-analysis]. / Körperliches Training bei pulmonaler Hypertonie ­ ein systematisches Review mit Metaanalyse.

BACKGROUND: Pulmonary hypertension (PH) is defined as an elevation of mean pulmonary-arterial pressure by > 20 mmHg at rest, which may lead to right heart failure. Physical exercise has not been regularly recommended for PH patients for fear of symptom deterioration or occurrence of exercise-induced adverse events. METHODS: Three electronic databases were searched for randomized, controlled trials investigating exercise training in PH patients using the following keywords: "pulmonary hypertension" OR "pulmonary arterial hypertension" AND "exercise" OR "pulmonary rehabilitation" AND "randomized". RESULTS: Five studies involving 187 PH patients were included in this systematic review. Exercise programs lasted for 3 - 12 weeks (e. g. endurance training for 10 - 45 minutes; 60 - 80 % of the peak heart rate). PH patients significantly improved exercise capacity compared to controls in 6-minute walk distance (+ 45 m; 95 % CI: 26 m - 64 m) or peak oxygen consumption (+ 2.3 ml/kg/min; 95 % CI: 1.8 - 2.9 ml/kg/min), both p < 0.001. Also, physical and mental quality of life improved significantly by exercise training. No exercise-induced adverse events were observed. CONCLUSION: Supervised exercise training can safely and significantly improve physical performance and quality of life in clinically stable PH patients with optimal drug treatment. However, larger studies including a wider range of PH are mandatory.

[Medical care of adults with congenital heart diseases : Present and future]. / Medizinische Versorgung von Erwachsenen mit angeborenen Herzfehlern : Gegenwart und Zukunft.

Congenital heart diseases (CHD) are the most common types of congenital organ defects. Thanks to medical progress in congenital cardiology and heart surgery, most children with CHD reach adulthood. Despite primarily successful treatment residual and subsequent conditions as well as (non)cardiac comorbidities can influence the chronic course of the disease and lead to a higher morbidity and mortality. Adults with congenital heart disease (ACHD) in Germany are not tied to the healthcare structure despite the great need for aftercare. According to the results of the medical care of ACHD (MC-ACHD) study, ACHD centers and specialists in Germany are insufficiently perceived despite increased complication rates and the great need for specialist guidance. General practitioners and patients are not adequately informed about existing ACHD facilities. A better awareness of the ACHD problem should be created at the level of primary medical supply in order to optimize care and to reduce morbidity and mortality. Improved future-oriented patient care includes lifelong regular follow-up and the possibility of interdisciplinary, integrated medical care of CHD.

Prenatally Diagnosed Isolated Coronary Arterial Fistula Leading to Severe Complications at Birth.

Prenatal diagnosis of a huge coronary artery fistula between the left coronary artery and the right ventricle was made by Doppler echocardiography at 22 weeks of gestation. Progression of the dilated fistula was monitored throughout pregnancy. The size of the fistula increased enormously up to 11 mm. Death occurred at birth. Monitoring of these fetuses is essential as severe complications can occur during pregnancy or at birth.

Influence of gestational diabetes on fetal autonomic nervous system: a study using phase-rectified signal-averaging analysis.

OBJECTIVES: Maternal gestational diabetes mellitus (GDM) is known to influence fetal physiology. Phase-rectified signal averaging (PRSA) is an innovative signal-processing technique that can be used to investigate fetal heart signals. The PRSA-calculated variables average acceleration capacity (AAC) and average deceleration capacity (ADC) are established indices of autonomic nervous system (ANS) function. The aim of this study was to evaluate the influence of GDM on the fetal cardiovascular and ANS function in human pregnancy using PRSA. METHODS: This was a prospective clinical case-control study of 58 mothers with diagnosed GDM and 58 gestational-age matched healthy controls in the third trimester of pregnancy. Fetal cardiotocography (CTG) recordings were performed in all cases at entry to the study, and a follow-up recording was performed in 19 GDM cases close to delivery. The AAC and ADC indices were calculated by the PRSA method and fetal heart rate short-term variation (STV) by CTG software according to Dawes-Redman criteria. RESULTS: Mean gestational age of both groups at study entry was 35.7 weeks. There was a significant difference in mean AAC (1.97 ± 0.33 bpm vs 2.42 ± 0.57 bpm; P < 0.001) and ADC (1.94 ± 0.32 bpm vs 2.28 ± 0.46 bpm; P < 0.001) between controls and fetuses of diabetic mothers. This difference could not be demonstrated using standard computerized fetal CTG analysis of STV (controls, 10.8 ± 3.0 ms vs GDM group, 11.3 ± 2.5 ms; P = 0.32). Longitudinal fetal heart rate measurements in a subgroup of women with diabetes were not significantly different from those at study entry. CONCLUSIONS: Our findings show increased ANS activity in fetuses of diabetic mothers in late gestation. Analysis of human fetal cardiovascular and ANS function by PRSA may offer improved surveillance over conventional techniques linking GDM pregnancy to future cardiovascular dysfunction in the offspring. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Does postexercise modelled capillary blood flow accurately reflect cardiovascular effects by different exercise intensities?

Blood flow (BF) in exercising muscles is an important factor for exercise capacity. Recently, a non-invasive method to estimate capillary BF (Qcap ) was introduced. Using this method, the Fick principle is re-arranged by using relative differences in deoxygenated haemoglobin (ΔHHb) as a surrogate for arteriovenous O2 difference and pulmonary oxygen uptake (VO2 ) instead of muscular oxygen uptake. The aim of this study was to examine (I) the relationship between Qcap and exercise intensity during and following exercise, and (II) to critically reflect the Qcap approach. Seventeen male subjects completed six bouts of cycling exercise with different exercise intensities (40-90% peak oxygen uptake, VO2peak ) in randomized order. VO2 and ΔHHb were monitored continuously during the trail. Qcap was modelled bi-exponentially, and mean response time (MRT) was calculated during recovery as well as the dissociation of modelled VO2 and Qcap recovery kinetics (MRT/τVO2 ). End-exercise Qcap increased continuously with exercise intensity. This also applied to MRT. Postexercise MRT/τVO2 increased from 40 to 60% VO2peak but remained stable thereafter. The results show that Qcap response to exercise is linearly related to exercise intensity. This is presumably due to vasoactive factors like shear-stress or endothelial-mediated vasodilation. MRT/τVO2 shows that postexercise Qcap is elevated for a longer period than VO2 , which is representative for metabolic demand following exercise ≥70% VO2peak . This is a hint for prolonged local vasodilation. According to previous studies, Qcap could not be modelled properly in some cases, which is a limitation to the method and therefore has to be interpreted with caution.

End-exercise ΔHHb/ΔVO2 and post-exercise local oxygen availability in relation to exercise intensity.

Increased local blood supply is thought to be one of the mechanisms underlying oxidative adaptations to interval training regimes. The relationship of exercise intensity with local blood supply and oxygen availability has not been sufficiently evaluated yet. The aim of this study was to examine the effect of six different intensities (40-90% peak oxygen uptake, VO2peak ) on relative changes in oxygenated, deoxygenated and total haemoglobin (ΔO2 Hb, ΔHHb, ΔTHb) concentration after exercise as well as end-exercise ΔHHb/ΔVO2 as a marker for microvascular O2 distribution. Seventeen male subjects performed an experimental protocol consisting of 3 min cycling bouts at each exercise intensity in randomized order, separated by 5 min rests. ΔO2 Hb and ΔHHb were monitored with near-infrared spectroscopy of the vastus lateralis muscle, and VO2 was assessed. ΔHHb/ΔVO2 increased significantly from 40% to 60% VO2 peak and decreased from 60% to 90% VO2 peak. Post-exercise ΔTHb and ΔO2 Hb showed an overshoot in relation to pre-exercise values, which was equal after 40-60% VO2peak and rose significantly thereafter. A plateau was reached following exercise at ≥80% VO2peak . The results suggest that there is an increasing mismatch of local O2 delivery and utilization during exercise up to 60% VO2peak . This insufficient local O2 distribution is progressively improved above that intensity. Further, exercise intensities of ≥80% VO2peak induce highest local post-exercise O2 availability. These effects are likely due to improved microvascular perfusion by enhanced vasodilation, which could be mediated by higher lactate production and the accompanying acidosis.

Potential detection of low-dose transdermal testosterone administration in blood, urine, and saliva.

Administration of low amounts of endogenous hormones - so-called micro-dosages - are supposed to represent a major challenge in doping analysis. To model such a situation, we have studied transdermal administrations of 2.4 mg/24 h testosterone patches and examined various steroid concentrations in blood, urine, and saliva of 11 volunteers. Multiple samples were collected at t = 0, 3, 6, 9, 24, 48, and 72 h in four different phases, i.e., all combinations with/without physical exercise and with/without testosterone. Testosterone was analyzed by enzyme-linked-immuno-assay as well as by mass spectrometry and validated in an accredited anti-doping laboratory. Circadian controls with and without exercise did not provoke prominent alterations of whole, free, and salivary testosterone. Testosterone application for 24 h led to a significant (all p < 0.001) mean increase above controls: total testosterone (median: 5.2 vs. 8.0 ng/mL), free testosterone (median: 11.3 vs. 15.6 pg/mL), and salivary testosterone (median: 62.4 vs. 99.9 pg/mL). Additionally, all three testosterone measurements indicated significant correlations to each other (all r > 0.538, all p < .001). Circadian-matching showed peaking testosterone values after 6 h and 9 h, reaching highest augmentation up to 252.6 ± 123.5% in saliva after 9 h. After removal of the testosterone patch, all testosterone levels in blood, saliva, and urine returned to baseline within 24 h. Different techniques of hormone detection (enzyme-linked immunosorbent assay (ELISA), gas chromatography-tandem mass spectrometry (GC-MS/MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS)) indicated significant correlations. Results indicate that saliva, blood, and urine exhibit comparable hormone augmentation during micro-dose testosterone application, indicating a possible consideration in future doping analysis. The inter-individual variability was high in all biofluids, requiring the use of an individual biological passport rather than statistical values. Copyright © 2016 John Wiley & Sons, Ltd.

Association between muscular strength and inflammatory markers among elderly persons with cardiac disease: results from the KORA-Age study.

Little is known about the association between muscle strength and inflammation in diseased individuals and particularly in cardiac patients. Thus, our purpose was to examine the association of muscular strength with the inflammatory status in older adults with and without cardiac disease. The cross-sectional analysis was based on 1079 adults aged 65-94 years, who participated in the KORA-Age study. Participants underwent an interview and extensive physical examinations including anthropometric measurements, registration of diseases and drug intake, determination of health-related behaviors, collection of blood samples for measurements of interleukin-6 and hs-CRP and muscle strength measurement using hand-grip dynamometry. Cardiac patients (n = 323) had higher levels of IL-6 and poorer muscle strength compared with older adults without cardiac disease. Among persons with cardiac diseases, muscle strength in the lower tertile compared to the upper tertile was significantly associated with increased odds of having elevated IL-6 levels (OR 3.53, 95 % CI 1.18-10.50, p = 0.024) after controlling for age, gender, body fat, alcohol intake, smoking status, diseases, medications and physical activity, whereas the association between muscle strength and hs-CRP remained borderline significant (OR 2.80, 95 % CI 0.85-9.24, p = 0.092). The same trends, with slightly lower odds ratios, were also observed in older adults without cardiac disease. Lower levels of muscular strength are associated with higher concentrations of IL-6 and hs-CRP in elderly individuals with and without cardiac disease suggesting a significant contribution of the muscular system in reducing low-grade inflammation that accompanies cardiac disease and aging.

Cardiac Adaptation of the Maternal Heart During Pregnancy: A Color-Coded Tissue Doppler Imaging Study--Feasibility, Reproducibility and Course during Pregnancy.

PURPOSE: Tissue Doppler imaging (TDI) allows the noninvasive quantification of global and regional myocardial function. Since there are changing loading conditions during pregnancy, this study aimed to determine maternal myocardial adaptation in normal pregnancy with TDI and tracking of the heart cycle. PATIENTS AND METHODS: 106 pregnant women, mean age of 33.4 years at baseline, prospectively underwent a total of 161 color-coded tissue Doppler echocardiography samples throughout pregnancy. In further offline analysis of the global and regional myocardial function of the basal segments, maximum tissue velocities at systole (Sm), in the early filling phase of diastole (Em) and during atrial contraction (Am) were assessed. RESULTS: From those stored samples, S-wave, E-wave and A-wave velocities could be obtained with a feasibility of 94.8 % and with good inter- and intra-observer variability. S-wave velocity first showed an increase during early pregnancy followed by a decline to baseline characteristics at the 3 rd trimester. The E-wave velocity declined throughout pregnancy. The A-wave velocity increased continuously. These alterations result in a continuous decline of Em/Am ratio as pregnancy advances. CONCLUSION: Alterations in tissue velocities during pregnancy reflect maturational changes that mimic "diastolic dysfunction". Based on an understanding of those normal physiological changes, TDI may therefore assist in the monitoring and/or detecting of subclinical myocardial dysfunction during pregnancy.

[Cyclic movement training versus conventional physiotherapy for rehabilitation of hemiparetic gait after stroke: a pilot study]. / Zyklisches apparatives Bewegungstraining versus konventionelles Gangtraining in der Rehabilitation des hemiparetischen Ganges nach Schlaganfall: Eine Pilotstudie.

BACKGROUND: Recovery of impaired motor functions following stroke is commonly incomplete in spite of intensive rehabilitation programmes. At 6 months following a stroke up to 60 % of affected individuals still suffer from permanent motor deficits, in particular hemiparetic gait, that are relevant for daily life. Novel innovative therapeutic strategies are needed to enhance the recovery of impaired gait function following stroke. METHOD: This pilot study has investigated the effectiveness of conventional physiotherapy in comparison to an apparative cyclic movement training over a period of 4 weeks to improve (i) power during a submaximal cyclic movement training of the lower limbs, (ii) cardiac fitness, (iii) balance and gait ability, and (iv) quality of life in stroke patients. RESULTS: In comparison to physiotherapy apparative cyclic movement training improved power, balance, cardiac fitness and quality of life to a greater extent. However, there was a statistically significant difference between both intervention groups only for balance but not for the other parameters assessed. CONCLUSION: The present pilot study should inspire future research with larger patient cohorts to allow appropriate judgement on the effectiveness of apparative cyclic movement training in stroke rehabilitation.

3-Dimensional sonographic volumetry of fetal brain, liver and myocardial mass--interdisciplinary clinical validation of the method and application in fetuses with and without structural heart disease.

BACKGROUND: Prenatal 3-dimensional (3D) ultrasound allows volumetry of the fetal brain, liver and measurement of myocardial mass (MM). We studied the reliability of this method in an interdisciplinary approach, defined the relation of the values throughout gestation, and evaluated the results in fetuses with congenital heart disease (CHD). METHODS: In 104 fetuses (39 with CHD) between 14 and 38 weeks of gestation 3D ultrasound was prospectively performed. Data sets of brain, abdomen and heart were stored for off-line analysis of volumes and MM. Descriptive statistics, coefficients of correlation and of variation (CV) were performed. RESULTS: Volumetric data set acquirement was feasible in all pregnancies, lasted approximately 10 min, but off-line analysis was feasible in only 66% lasting about 45 min. MM increased in a linear fashion during gestation. CV were 11.0 and 10.8 for the left, 14.39 and 12.66, respectively, for the right MM. Median ratio between right and left MM was 0.88 in normal fetuses, and 8.25 in fetuses with hypoplastic left heart syndrome. Intra- and interobserver variabilities revealed CVs of 2.46 and 11.80, respectively, for brain volumetry, and CVs of 3.16 and 29.2, respectively, for liver volumetry. Both brain and liver volumes were positively associated with gestational age, and did not show different growth patterns in fetuses with CHD. CONCLUSIONS: Prenatal volumetry is time-consuming, but reliable especially for left MM and brain volume. Linear growth of brain and liver volume is present in utero irrespective of CHD. Application of our reference graphs of MM growth allows early differentiation in CHD.

Reversible foetal cerebral ventriculomegaly and cardiomyopathy under chemotherapy for maternal AML.

BACKGROUND: Leukaemia in pregnancy is a rare complication demanding a multidisciplinary approach and careful management to handle potential complications and cope with ethical dilemmas. PATIENT AND METHODS: We report on a patient with acute myeloid leukaemia (AML) relapse in 22 weeks of gestation who received chemotherapy with cytarabine and mitoxantrone, as well as fludarabine, cytarabine, idarubicin, and gemtuzumabozogamicin. We describe findings on regular ultrasound examinations and successful management of complications. RESULTS: The foetus developed signs of anthracycline-induced cardiomyopathy, transient cerebral ventriculomegaly, anaemia, and intrauterine growth restriction. The child was delivered by Caesarean section at 33 + 1 weeks of gestation. The newborn showed no congenital malformations. CONCLUSION: This case report confirms that chemotherapy for treatment of AML can be applied in the second trimester of pregnancy under close and careful maternal and foetal monitoring.

Sample volume positioning in colour-coded Doppler myocardial imaging: effect of systolic and diastolic tracking.

To date, Doppler myocardial imaging (DMI) is no longer an intriguing new research tool only, but is rather on the verge of becoming a routinely used diagnostic method in adult and pediatric cardiology. Clinical studies have proven its diagnostic relevance for global left and right ventricular function. Concerns about reliability and reproducibility of DMI functional analysis, however, rely on lacking standards for the acquisition and analysis of DMI parameters. This study focuses on the effect of sample volume positioning during the cardiac cycle on the absolute myocardial velocities. Our hypothesis was that systolic sample volume placement leads to altered diastolic measurements, and diastolic placement vice versa to altered systolic measurements, when compared with continuous systolic and diastolic tracking. The effect of tracking on intra- and interobserver variability was a second endpoint of the study. Twenty healthy women underwent color-coded Doppler myocardial imaging. Clips of three heart cycles were stored in digital format for off-line analysis, administering sector angles of approximately 30 degrees and a mean frame rate of 280 frames per second. Using the Echopac software (GE, Germany), the sample volume was positioned immediately below the atrioventricular valvar annulus within the basal segments of the right and left ventricular free wall and the interventricular septum. Three conditions were investigated: conventional end-systolic or end-diastolic placement of the Doppler probe, or continuous tracking to the ideal position during systole or diastole. Descriptive statistics, intra and interobserver variabilities and Bland-Altman analyses were performed. Tracking revealed higher values of early diastolic myocardial velocities compared with measurements during systolic sample volume placement only, and higher systolic myocardial velocities, preejection acceleration and late diastolic myocardial velocities using diastolic sample volume placement. Inter and intraobserver reproducibility improved remarkably with the new procedure with the exception of isovolumic acceleration (IVA), which could not be reproduced satisfactorily at all. In summary, tracking is a promising method that helps to improve reproducibility of DMI-derived myocardial velocities. It helps to minimize the effect of changing myocardial velocities during the natural longitudinal cardiac movement, and should be considered as standard method during DMI.

In vivo intrauterine sound pressure and temperature measurements during magnetic resonance imaging (1.5 T) in pregnant ewes.

OBJECTIVE: To investigate the influence of several magnetic resonance imaging (MRI) sequences on amniotic fluid temperature and intrauterine sound pressure. MATERIAL AND METHODS: Temperature and sound pressure measurements during MRI (1.5 T) in pregnant ewes were done. Linear levels and third octave band spectra were compared. RESULTS: No significant changes in the temperature of amniotic fluid were observed. Intrauterine summation levels reached peak levels up to 103.0 dB(A) before starting the MRI sequence and levels up to 116.0 dB(A) during a real-time sequence. Evaluating the octave band spectra, peak levels did not exceed 100.0 dB(L). CONCLUSIONS: Our delimited data revealed no harm for the fetus by an increase in amniotic fluid temperature or hazards for the fetal auditory system by different MRI sequences.

Prenatal constriction of the fetal ductus arteriosus--related to maternal pain medication?

Physiological fetal circulation requires patency of the ductus arteriosus. As gestation proceeds, the sensitivity of the ductus to dilating prostaglandins diminishes. The sensitivity to constricting agents like PGE-synthetase inhibitors, present in many analgetics, however, increases. Fetuses affected by an antenatal constriction of the ductus arteriosus (DC) may present with different signs of cardiac failure including dilated right ventricle, tricuspid regurgitation and abnormal venous Doppler. We report on four cases with prenatal DC, presenting at 34, 35, 36 and 37 weeks of gestation. They were referred to fetal echocardiography because of abnormal routine echo scans with unexplained signs of right heart decompensation. Three patients were medicated during pregnancy with either aspirin (low dose), metamizole or ibuprofen. One patient did not take any drugs, especially no pain medication drug in pregnancy. Immediate delivery was performed in all cases. The neonates were in a good condition; echocardiography showed different degrees of right heart hypertrophy which disappeared in all infants by the age of 3 months except in case 2. Unexplained fetal right heart decompensation requires detailed echocardiographic evaluation of the ductus arteriosus and a sophisticated medical history with regard to analgesics. In contrast to ibuprofen and high-dose aspirin, metamizole and low-dose aspirin have not yet been reported as possible agents constricting the fetal arterial duct. In any suspected context, early delivery as in our cases may save babies life. Any application of non-steroidal anti-inflammatory drugs in pregnancy requires close fetal follow-up due to their potentially life-threatening effect.

Aortopulmonary window with ventricular septal defect and pulmonary atresia: prenatal diagnosis and successful early surgical correction.

We report a case in which aortopulmonary window (APW) in combination with pulmonary atresia was diagnosed correctly in a neonate by echocardiography. Prenatal echocardiography showed progression of tetralogy of Fallot to pulmonary atresia with retrograde pulmonary perfusion, concealing the concomitant APW in fetal life. Due to intractable heart failure, primary correction was successfully performed at the age of 4 weeks (weight 2280 g).

Fatal propofol infusion syndrome in association with ketogenic diet.

Propofol is used for the treatment of refractory status epilepticus. When given as a long-term infusion propofol may cause a rare but frequently fatal complication, the propofol infusion syndrome. The hallmarks are metabolic acidosis, lipemia, rhabdomyolysis and myocardial failure. Propofol infusion syndrome is caused by impaired fatty acid oxidation. Beside anticonvulsants the ketogenic diet, a high-fat, low-carbohydrate, adequate-protein diet, is an effective treatment for difficult-to-control seizures. We report a 10-year-old boy with catastrophic epilepsy, who developed fatal propofol infusion syndrome when a ketogenic diet was initiated. Substances like propofol which impair fatty acid oxidation may pose an increased risk if combined with ketogenic diet.