Ulrike Müller

Randomized Sham-Controlled Trial of Renal Sympathetic Denervation in Mild Resistant Hypertension

Few data are available with regard to the effectiveness of renal sympathetic denervation in patients with resistant hypertension yet only mildly elevated blood pressure (BP). Patients with resistant hypertension and slightly elevated BP (day-time systolic pressure, 135–149 and diastolic pressure, 90–94 mm Hg on 24-hour ambulatory measurement) were randomized in a 1:1 ratio to renal sympathetic denervation with the Symplicity Flex Catheter (Medtronic) or an invasive sham procedure. The primary efficacy end point was the change in 24-hour systolic BP at 6 months between groups in the intention to treat population. A total of 71 patients underwent randomization. Baseline day-time systolic BP was 144.4±4.8 mm Hg in patients assigned to denervation and 143.0±4.7 mm Hg in patients randomized to the sham procedure. The mean change in 24-hour systolic BP in the intention to treat cohort at 6 months was −7.0 mm Hg (95% confidence interval, −10.8 to −3.2) for patients undergoing denervation and −3.5 mm Hg (95% confidence interval, −6.7 to −0.2) in the sham group (P=0.15). In the per protocol population, the change in 24-hour systolic BP at 6 months was −8.3 mm Hg (95% confidence interval, −11.7 to −5.0) for patients undergoing denervation and −3.5 mm Hg (95% confidence interval, −6.8 to −0.2) in the sham group (P=0.042). In patients with mild resistant hypertension, renal sympathetic denervation failed to show a significant reduction in the primary end point of 24-hour systolic BP at 6 months between groups in the intention to treat analysis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01656096.

Serum irisin levels are regulated by acute strenuous exercise.

RATIONALE The newly discovered myokine irisin has been proposed to affect obesity and metabolism by promoting browning of white adipose tissue. However, clinical and functional studies on the association of irisin with obesity, muscle mass, and metabolic status remain controversial. Here we assessed the effect of 4 distinct exercise regimens on serum irisin levels in children and young adults and systematically evaluated the influence of diurnal rhythm, anthropometric and metabolic parameters, and exercise on irisin. RESULTS Serum irisin levels did not show diurnal variations, nor were they affected by meal intake or defined glucose load during oral glucose tolerance testing. Irisin levels decreased with age. In adults, irisin levels were higher in men than in women, and obese subjects had significantly higher levels than lean control subjects. Irisin levels were closely correlated with muscle-associated bioimpedance parameters such as fat-free mass and body cell mass. Of the 4 exercise regimens that differed in duration and intensity, we identified a clear and immediate increase in serum irisin levels after acute strenuous exercise (cycling ergometry) and a 30-minute bout of intensive exercise in children and young adults, whereas longer (6 weeks) or chronic (1 year) increases in physical activity did not affect irisin levels. SUMMARY We show that irisin levels are affected by age, sex, obesity, and particularly muscle mass, whereas diurnal rhythm and meals do not contribute to the variation in irisin levels. Short bouts of intensive exercise but not long-term elevations in physical activity, acutely and transiently increase serum irisin levels in children and adults.

Impaired HDL function in obese adolescents: Impact of lifestyle intervention and bariatric surgery

HDL regulates endothelial function via stimulation of nitric oxide production. It is documented that endothelial function is impaired in obese adolescents, and improved by lifestyle interventions (LI).

Invasive aortic pulse wave velocity as a marker for arterial stiffness predicts outcome of renal sympathetic denervation.

AIMS A recurrent finding of trials on renal sympathetic denervation is a certain percentage of non-responders. The aim of this study was to examine the influence of arterial stiffness to predict response. METHODS AND RESULTS Eighty-eight patients were included in the study. Arterial stiffness was measured by invasive pulse wave velocity. Antihypertensive medication had to be unchanged during follow-up. Ambulatory blood pressure measurement (ABPM) was used to record blood pressure before and six months after denervation. Fifty-eight patients without changes in medication were included in the final analysis. Responders (n=37; blood pressure reduction -12.8±6.4 mmHg) had a significantly lower pulse wave velocity (14.4±4.4 m/s versus 17.7±4.5 m/s; p=0.009) compared to non-responders (n=21; blood pressure reduction +3.0±4.5 mmHg; p<0.001 for comparison with responders). In multivariate analysis, invasive pulse wave velocity was the only significant predictor of blood pressure reduction after denervation (odds ratio 1.15, 95% confidence interval [CI] 1.014-1.327; p=0.03). Patients with increased stiffness were older (p=0.001), had a higher prevalence of diabetes (p=0.008), more often had isolated systolic hypertension (p=0.007), and had a higher invasive pulse pressure (p<0.001). CONCLUSIONS Patients with lower pulse wave velocity showed a significantly better response to denervation. These findings emphasise that pulse wave velocity might be used as a selection criterion for renal denervation.

Correlation between endothelial function measured by finger plethysmography in children and HDL-mediated eNOS activation — a preliminary study

BACKGROUND The noninvasive measurement of endothelial function is a very powerful tool to assess cardiovascular disease. Especially in children this is not an easy task, and therefore an easy method like the Endo-Pat device is helpful. Due to the still existing uncertainties of the validity of endothelial measurement by the Endo-PAT device in children, we thought to analyze the correlation between endothelial functional measurement by Endo-PAT, and the capability of HDL to modify nitric oxide (NO) production by phosphorylation of endothelial nitric oxide synthase at the stimulatory site (Ser(1177)) and the inhibitory site (Thr(495)). METHODS The reactive hyperemic index (RHI) was measured in 11 school children by the Endo-PAT device. HDL was isolated by ultracentrifugation, and the capability to stimulate eNOS phosphorylation was assessed in cell culture. RESULTS A close correlation between the RHI and the eNOS-Ser(1177) phosphorylation (r=0.66, p=0.02) and the eNOS-Thr(495) phosphorylation (r=-0.60, p=0.04) was detected. CONCLUSION The results obtained in our limited study performed in healthy children supports the validity of endothelial function measurement in children using the Endo-PAT device. Nevertheless, studies measuring FMD and the RHI index need to confirm the strength of the Endo-Pat device also in children.

Endocardial Calcification of Left Atrium, Tracheobronchopathia Osteoplastica, and Calcified Aortic Arch in a Patient With Dyspnea

A 69-year-old female patient was admitted to our hospital for further cardiac evaluation with symptoms of dyspnea (New York Heart Association class III) and peripheral edema. Her history revealed artificial mitral valve replacement due to mitral stenosis 8 years earlier, severe chronic pulmonary hypertension, and severe tricuspid valve incompetence. Electrocardiogram showed normofrequent atrial fibrillation. Transthoracic echocardiography indicated moderate biatrial enlargement, although both ventricles had normal dimensions and normal global systolic function. The transmitral prosthetic valve gradient was 14/6 mm Hg. We documented severe tricuspid regurgitation and only mild mitral regurgitation. Nevertheless, echocardiography was difficult to perform because of lack of an adequate acoustic window and metal artifacts of the mitral valve prosthesis. Reflections at the epicardial surface close to the mitral valve were therefore interpreted as calcifications of pericardial layer, and constrictive pericarditis was expected to be the most likely cause of the patient’s symptoms and diastolic left ventricle dysfunction. By right heart catheterization, severe postcapillary hypertension was confirmed (systolic/diastolic/mean pulmonary …

Long term impact of one daily unit of physical exercise at school on cardiovascular risk factors in school children

Background Obesity and physical inactivity in children correlate with the presence of cardiovascular risk factors. The aim of this prospective, randomised, interventional study was to examine the long term impact of additional physical exercise lessons at school on fitness and cardiovascular risk factors. Methods We randomly assigned 366 5th and 6th grade students class-wise into an intervention group that participated in one-daily physical exercise unit at school and a control group, participating in conventional school sports twice a week. The intervention duration was 4 years. At baseline and yearly follow-up, anthropometric measurements, body coordination tests, spiroergometry, questionnaires and blood samples were performed. Results A total of 236 children qualified for analysis of the intervention effect after 4 years. At the beginning students of the intervention and control groups had similar values for fitness assessed by peak oxygen uptake. Peak oxygen uptake was significantly better in the intervention group at first and second follow-up. After 4 years we found no difference in fitness any longer. Students in the intervention group were more likely to have healthy body mass index percentiles in comparison to the control group (within 10th to 90th percentile: intervention 86.4%, control 78.2%, P = 0.13). Conclusion Over a period of 1–2 years, additional physical exercise lessons at school resulted in an improvement of fitness. However, long-term follow-up failed to demonstrate ongoing improvement of performance in the intervention compared with the control group. Nevertheless, the intervention group had lower rates of body mass index above the 90th percentile throughout the entire follow-up. Therefore more physical exercise units at school seem justified.

Cardiac valve degeneration in a patient with Sneddon syndrome

Sneddon syndrome—a rare cause of aortic and mitral valve stenosis. Sneddon syndrome is a rare disorder that leads to repeated occurrence of cerebrovascular disease and skin manifestation, defined as livedo racemosa generalisata. The authors report the occurrence of multiple valve degenerations in a 49-year-old patient with Sneddon syndrome, which seemed to have been asymptomatic through a long period of time and was diagnosed as it needed a complex surgical intervention.

Reliability of the calculated maximal lactate steady state in amateur cyclists

Complex performance diagnostics in sports medicine should contain maximal aerobic and maximal anaerobic performance. The requirements on appropriate stress protocols are high. To validate a test protocol quality criteria like objectivity and reliability are necessary. Therefore, the present study was performed in intention to analyze the reliability of maximal lactate production rate (V.Lamax) by using a sprint test, maximum oxygen consumption (V.O2max) by using a ramp test and, based on these data, resulting power in calculated maximum lactate-steady-state (PMLSS) especially for amateur cyclists. All subjects (n = 23, age 26 ± 4 years) were leisure cyclists. At three different days they completed first a sprint test to approximate V.Lamax. After 60 min of recreation time a ramp test to assess V.O2max was performed. The results of V.Lamax-test and V.O2max-test and the body weight were used to calculate PMLSS for all subjects. The intra class correlation (ICC) for V.Lamax and V.O2max was 0.904 and 0.987, respectively, coefficient of variation (CV) was 6.3% and 2.1%, respectively. Between the measurements the reliable change index of 0.11 mmol·l -1s -1 for V.Lamax and 3.3 mlkg -1min -1 for V.O2max achieved significance. The mean of the calculated PMLSS was 237 ± 72 W with an RCI of 9 W and reached with ICC = 0.985 a very high reliability. Both metabolic performance tests and the calculated PMLSS are reliable for leisure cyclists.

Gerbode ventricular septum defect covered by a ballooning membranous ventricular septum

A 55-year-old man was admitted due to a new cardiac murmur diagnosed by his general practitioner during check-up. The patient was asymptomatic and denied chest pain or dyspnea. Physical examination revealed a grade 3/6 holosystolic heart murmur at the left sternal border with increased intensity to handgrip maneuvers. In addition, mild edema was present at his ankles up to mid of the lower legs that the patient himself had not recognized before. Electrocardiogram, blood sample, and cardiac markers were unremarkable. Transthoracic echocardiography (TTE) revealed enlargement of heart chambers with normal systolic ventricular function and elevated pulmonary pressure. In addition, a cystic thin walled structure was seen with adhesion at the septal tricuspid valve ring that yo-yoed between the right atrium (RA) and the right ventricle (RV) like a table tennis ball. Colour Doppler echocardiography showed a complete systolic filling of this structure. Diagnostic work-up revealed a congenital defect of subaortic perimembranous ventricle septum (VSD) with conjunction between left ventricle (LV) and RA, a so-called Gerbode-VSD, covered by a prolapsing cystic formation of 38 9 29 9 27 mm (Figs. 1, 2). By MRI and heart catheterization, a relevant left-to-right shunt of 1:2 was measured. Hemodynamic parameters are given in Table 1. MRI confirmed a perforation of the cystic sack causing the shunt with direct flow to RA (Fig. 2b). Surgery under cardiopulmonary bypass was undertaken and revealed a right sided whitish cystic mass typical for a large diverticulum of the membranous ventricular septum with basis above the tricuspid valve and riding above a Gerbode-VSD of 6 mm. Opposite to the VSD, the cystic structure was perforated resulting in a direct communication between LV and RA (Figs. 2b and 3a, b). The diverticulum was removed, VSD was closed with a bovine pericardial patch and the tricuspid valve was successfully reconstructed. Pathohistologic inspection of the cystic structure showed endoand myocardium with fibrotic and sclerotic conversion and only mild chronic inflammatory reaction (Fig. 3c). Patient was discharged in stable conditions 10 days after surgery. The specific feature of our patient is the coverage of the Gerbode-VSD by the expanded membranous ventricular septum protruding into the RA with extension through the tricuspid valve during heart cycle. A small rupture of the cystic formation caused a nearly indirect shunt between LV and RA. Shunts between LV and RA are rare forms of VSD and can be either congenital or acquired. They were first described in 1857 and represent \1 % of all congenital cardiac defects [1]. The surgeon Frank Gerbode at Stanford had published the first successful series of patients operated on a LV–RA shunt in 1958 [2]. Acquired defects can occur secondarily after bacterial endocarditis, trauma, myocardial infarction, repair or replacement of either the mitral or aortic valves or are reported after catheter ablation of the atrioventricular node [1, 3–7] and are diagnosed using varying U. M. Muller (&) U. Pittl G. C. Schuler Department of Internal Medicine/Cardiology, Heart Center, University of Leipzig, Strumpellstrase 39, 04289 Leipzig, Germany e-mail: ulrike.mueller@herzzentrum-leipzig.de