[From myxomas of the skin to LVAD implantation : A 28-year-old female patient with Carney complex]. / Von Hautmyxomen zur LVAD-Implantation : Eine 28-jährige Patientin mit Carney-Komplex.

Multiple skin lesions, endocrine dysfunction and cardiac myxomas are characteristic symptoms of Carney complex. This case report gives an overview about the major and minor criteria of Carney complex and presents the course of a female patient who developed severe cardiac insufficiency with multiple organ failure because of recurring heart operations leading to implantation of a left ventricular assist device (LVAD).

Role of Experience, Leadership and Individual Protection in the Cath Lab--A Multicenter Questionnaire and Workshop on Radiation Safety.

PURPOSE: Radiation exposure in invasive cardiology remains considerable. We evaluated the acceptance of radiation protective devices and the role of operator experience, team leadership, and technical equipment in radiation safety efforts in the clinical routine. MATERIALS AND METHODS: Cardiologists (115 from 27 centers) answered a questionnaire and documented radiation parameters for 10 coronary angiographies (CA), before and 3.1 months after a 90-min. mini-course in radiation-reducing techniques. RESULTS: Mini-course participants achieved significant median decreases in patient dose area products (DAP: from 26.6 to 13.0 Gy × cm(2)), number of radiographic frames (-29%) and runs (-8%), radiographic DAP/frame (-2%), fluoroscopic DAP/s (-39%), and fluoroscopy time (-16%). Multilevel analysis revealed lower DAPs with decreasing body mass index (-1.4 Gy × cm(2) per kg/m(2)), age (-1.2 Gy × cm(2)/decade), female sex (-5.9 Gy × cm(2)), participation of the team leader (-9.4 Gy × cm(2)), the mini-course itself (-16.1 Gy × cm(2)), experience (-0.7 Gy × cm(2)/1000 CAs throughout the interventionalist's professional life), and use of older catheterization systems (-6.6 Gy × cm(2)). Lead protection included apron (100%), glass sheet (95%), lengthwise (94%) and crosswise (69%) undercouch sheet, collar (89%), glasses (28%), cover around the patients' thighs (19%), foot switch shield (7%), gloves (3%), and cap (1%). CONCLUSION: Radiation-protection devices are employed less than optimally in the clinical routine. Cardiologists with a great variety of interventional experience profited from our radiation safety workshop - to an even greater extent if the interventional team leader also participated. KEY POINTS: Radiation protection devices are employed less than optimally in invasive cardiology. The presented radiation-safety mini-course was highly efficient. Cardiologists at all levels of experience profited from the mini-course - considerably more so if the team leader also took part. Interventional experience was less relevant for radiation reduction. Consequently both fellows and trainers should be encouraged to practice autonomy in radiation safety.

ECG-gated coronary angiography enables submillisievert imaging in invasive cardiology.

BACKGROUND: The median dose area products (DAP) and effective doses (ED) of patients arising from coronary angiography (CA) are considerable: According the 2013 National German Registry, they amount to 19.8 Gy × cm(2) and 4.0 mSv, respectively. METHODS: We investigated the feasibility of prospective electrocardiogram (ECG)-gated coronary angiography (CA)-a novel technique in invasive cardiology-with respect to possible reduction in irradiation effects. Instead of universally fix-rated radiographic acquisition within 7.5-15 frames/s, one single frame/heartbeat was triggered toward the diastolic moment immediately before atrial contraction (77 % of ECG-RR interval) most likely to provide motion-free and hence optimized resolution of the coronary tree. For 200 patients (body mass index 27.8 kg/m(2), age 67.5 years, male 55 %, 68 bpm) undergoing ECG-gated CA, we measured various median (interquartile range) parameters for radiation exposure. RESULTS: The total DAP was 0.64 (0.46-1.00), radiographic fraction was 0.30 (0.19-0.43), and fluoroscopic fraction was 0.35 (0.21-0.57) Gy × cm(2). Radiographic imaging occurred within 21.7 s (17.1-26.3), with 25 frames (20-30) over the course of 7 runs (6-8). Fluoroscopy time was 119 s (94-141). Radiographic DAP was 12.6 mGy × cm(2)/frame and 13.8 mGy × cm(2)/s. Fluoroscopic DAP was 0.8 mGy × cm(2)/pulse and 3.1 mGy × cm(2)/s. Patient reference point air kerma was 17.0 mGy (11.1-28.1) and contrast volume was 70 ml (60-85). CONCLUSION: In conclusion, invasive ECG-gated coronary imaging is feasible in clinical routine and enables patient EDs of approx. 3 % of typical values in invasive cardiology: 0.13 mSv (0.09-0.20).

Latest-generation catheterization systems enable invasive submillisievert coronary angiography.

BACKGROUND: The radiation risk of patients undergoing invasive cardiology remains considerable and includes skin injuries and cancer. To date, submillisievert coronary angiography has not been considered feasible. PATIENTS AND METHODS: In 2011, we compared results from 100 consecutive patients undergoing elective coronary angiography using the latest-generation flat-panel angiography system (FPS) with results from examinations by the same operator using 106 historic controls with a conventional image-intensifier system (IIS) that was new in 2002. RESULTS: The median patient exposure parameters were measured as follows: dose-area product (DAP) associated with radiographic cine acquisitions (DAP(R)) and fluoroscopy (DAP(F)) scenes, radiographic frames and runs, and cumulative exposure times for radiography and fluoroscopy. On the FPS as compared to the traditional IIS, radiographic detector entrance dose levels were reduced from 164 to 80 nGy/frame and pulse rates were lowered from 12.5/s to 7.5/s during radiography and from 25/s to 4/s during fluoroscopy. The cardiologist's performance patterns remained comparable over the years: fluoroscopy time was constant and radiography time even slightly increased. Overall patient DAP decreased from 7.0 to 2.4 Gy × cm(2); DAP(R), from 4.2 to 1.7 Gy × cm(2); and DAP(F), from 2.8 to 0.6 Gy × cm(2). Time-adjusted DAP(R)/s decreased from 436 to 130 mGy × cm(2) and DAP(F)/s, from 21.6 to 4.4 mGy × cm(2). Cumulative patient skin dose with the FPS amounted to 67 mGy, and the median (interquartile range) of effective dose was 0.5 (0.3 … 0.7) mSv. CONCLUSION: Consistent application of radiation-reducing techniques with the latest-generation flat-panel systems enables submillisievert coronary angiography in invasive cardiology.

[Diagnosis of systolic and diastolic heart failure]. / Diagnostik der systolischen und diastolischen Herzinsuffizienz.

In this review, heart failure is confined to etiologies not due to rhythm disturbances or valvular heart disease. Besides measurement of natriuretic peptides, echocardiography is established as an important diagnostic procedure. Echocardiography is especially helpful in discriminating between heart failure with preserved ejection fraction (HF-PEF) and reduced ejection fraction (HF-REF). Because of its ease to be performed, the 6 min walk test continues to be a standard diagnostic procedure. Cardiopulmonary exercise testing provides more detailed information regarding differential diagnostic and prognostic considerations.

Long-term efficacy of a mini-course in radiation-reducing techniques in invasive cardiology.

PURPOSE: To validate the long-term efficacy of a 90-min. educational mini-course in less-irradiating cardiac interventional techniques. MATERIALS AND METHODS: Before, two months after, and two years after the mini-course (periods I, II, and III), we analyzed the following radiation dose parameters for ten coronary angiographies (CA), performed by each of 7 cardiologists: total dose-area product (DAP), radiographic and fluoroscopic DAP fractions, number of radiographic frames and runs, and fluoroscopy time. RESULTS: The median patient DAP for periods I, II and III was 31.4, 15.8 and 8.5 Gy × cm2, respectively. The long-term effect was related to shorter median fluoroscopy times (180, 172, and 120 s), shorter (57, 52, and 45) and fewer (12, 12, and 10) radiographic runs, consistent collimation and restriction to an adequate image quality. Both radiographic DAP/frame (28.7, 17.0, and 18.4 mGy × cm2) and fluoroscopic DAP/second (45.7, 24.2, and 10.0 mGy × cm2) decreased significantly. The multivariate linear regression analysis confirmed the increasing efficacy of the mini-course itself (-44.6 and -60.7%), and revealed a decreasing influence of the interventionalist's experience (-8.6% and -4.9% per 1,000 CAs, lifelong performed until the mini-course). The number of CAs performed after the mini-course did not influence the long-term DAP results. CONCLUSION: The presented educational mini-course allows a significant, long-lasting, and apparently ongoing reduction of patient radiation exposure due to CA. A self-surveillant documentation of relevant radiation parameters is well suited to monitor and improve each operator's individual long-term radiation-reducing efforts.

Initial white blood cell count is an independent risk factor for survival in patients with dilated cardiomyopathy.

BACKGROUND: The impact of white blood cell count (WBCc) on the outcome of patients with non-ischemic left ventricular (LV) dysfunction is unknown. In the present study we investigated the influence of WBCc on mortality and cardiac inflammation in patients with reduced LV systolic function in the absence of ischemic or valvular etiology. METHODS AND RESULTS: We included 381 patients with reduced left ventricular (LV) ejection fraction (LVEF ≤ 45%) quantified by two-dimensional echocardiography. Coronary artery disease and valvular diseases were excluded by angiography and echo, respectively, in all patients. WBCc was quantified routinely upon first hospital admission. In 291 patients, endomyocardial biopsies from the right ventricle were performed upon first hospital admission for assessment of cardiac inflammation. Follow-up was up to 5.5 years (median 2.93 [1.7;4.0]). Information on vital status of patients was obtained from official resident data files. WBCc >11 Gpt/l was associated with significantly increased mortality in patients with severe LV dilation (end-diastolic diameter (LVEDD) >70 mm quantified by echocardiography) in comparison to patients showing WBCc ≤ 11 Gpt/l (41.7% vs 13.6%, p=0.02). Multivariable Cox regression analysis showed that WBCc predicts mortality independently of other cardiovascular risk factors and LVEF (hazard ratio 1.14; p=0.04). Doses of heart failure medication did not differ significantly in patients with LVEDD >70 mm and WBCc >11 Gpt/l when compared to LVEDD >70 mm and WBCc ≤ 11 Gpt/l (percent of maximum doses: ß-blockers p=0.51, ACE inhibitors p=0.56, AT1 antagonists p=0.77, aldosterone antagonists p=0.35). WBCc including its subpopulations (monocytes, lymphocytes and granulocytes) did not show a significant correlation with cardiac amounts of CD3(+)-lymphocytes (r=0.02, p=0.78) or CD68(+)-macrophages (r=1.0, p=0.09) (n=291). CONCLUSION: WBCc at first hospital admission predicts long term-mortality in patients with dilated cardiomyopathy independently of cardiovascular risk factors.

Plasma aldosterone levels and aldosterone-to-renin ratios are associated with endothelial dysfunction in young to middle-aged subjects.

OBJECTIVE: Small clinical studies suggested a role for aldosterone in the development of endothelial dysfunction. We investigated whether the plasma aldosterone concentration (PAC) or the aldosterone-to-renin ratio (ARR) were associated with decreased endothelial function as measured by flow-mediated dilation (FMD) of the brachial artery in the general population. METHODS: Our study population comprised 972 participants from the Study of Health in Pomerania, who were not treated with antihypertensive medication. We performed age-stratified (<50 and ≥ 50 years) ordinal logistic regression analyses. FMD was categorised as decreased (1st quintile), moderate (2nd-4th quintile), or increased (5th quintile). PAC and ARR were divided into low, moderate, and high values according to age- and sex-specific tertiles. All models were re-calculated for 871 subjects with PAC and ARR within the study-specific reference ranges. Odds ratios (OR) and 95% confidence intervals (CI) are presented. RESULTS: Subjects <50 years with high PAC (OR 1.60; 95% CI 1.07-2.38) or ARR (OR 1.81; 95% CI 1.21-2.73) had higher odds for decreased FMD than subjects with low PAC or ARR, respectively. Similar results were obtained in analyses restricted to subjects with PAC and ARR within the reference range. High-normal PAC (OR 1.62; 95% CI 1.07-2.47) or ARR (OR 1.62; 95% CI 1.05-2.50) was associated with higher odds for decreased FMD when compared with low-normal PAC or ARR, respectively. These associations were not observed in subjects ≥ 50 years. CONCLUSIONS: High and high-normal PAC or ARR contribute to an impaired FMD and subsequently the progression of subclinical atherosclerosis in young to middle-aged subjects.

Radiation-reducing planning of cardiac catheterisation.

Any radiation exposition for medical purposes should be kept as low as is reasonably achievable. Mean patient radiation exposure of diagnostic cardiac catheterisation is high (16-106 Gy x cm2) and for this reason the International Commission on Radiological Protection (ICRP) recommends credentialing radiation protection training programmes. Twenty cardiologists each documented various dose parameters of 10 cardiac catheterisations, before and after a 90-minute mini-course of the ELICIT study group ("Encourage to Less Irradiating Cardiologic Interventional Techniques"), and could achieve a reduction of the mean dose-area product by 15.9+/-9.0 Gy x cm2, equivalent to 47%. The presented radiation-reducing planning of invasive cardiac catheterisation for this reason is the first one validated in clinical routine and consists of 6 standard runs--one for the left ventricle, 3 and 2 for the left (LCA) and right coronary artery (RCA), respectively--depending on anatomy and findings supplemented by 1...4 special projections. The caudal posteroanterior (PA) view documents the left coronary main stem, proximal and distal left anterior descending artery (LAD), and proximal and mid circumflex segments. The cranial PA view however is suitable for the left coronary orifice, circumflex periphery, LAD, all diagonal bifurcations, and collateral pathways towards the RCA. LCA standard angiography is completed by lateral 90 degrees/0 degrees left anterior oblique (LAO) angulation. The 60 degrees/0 degrees LAO angulation visualises the right posterolateral artery (RPL) and the RCA to its bifurcation. The more proximal one finds the bifurcation, the more the second standard cranial PA view for RCA should vary towards the cranial right anterior oblique (RAO) and finally 30 degrees/0 degrees RAO view. The efficiency of these less-irradiating angulations are improved by radiation-reducing techniques as follows: restriction to essential radiographic frames and runs, consistent collimation to the region of interest--particularly during coronary intubation--, adequate instead of best possible image quality, short skin-to-image-intensifier distance, inspiration during radiography, preference for projections that rotate out the spine, optimisation of fluoroscopy time, well-experienced and well-rested interventionists.

[Fluoroscopy time -- an overestimated factor for patient radiation exposure in invasive cardiology]. / Durchleuchtungszeit -- Ein überschätzter Parameter der Patientendosis in der invasiven Kardiologie.

PURPOSE: To analyze the effects of an optimized fluoroscopy time on patient radiation exposure in the course of coronary angiography (CA) and percutaneous coronary interventions (PTCA), in comparison to those with consistent collimation to the region of interest (ROI). Furthermore, to analyze efforts concerning reduction of radiographic frames as well as concerning adequate instead of best possible image quality. MATERIAL AND METHODS: For 3,115 elective CAs and 1,713 PTCA performed by one interventionist since 1997, we documented the radiographic dose-area products (DAP (R)) and fluoroscopic dose-area products (DAP (F)), the number of radiographic frames and the fluoroscopy times during selected 2-month intervals. Under conditions of constant image intensifier entrance dose, levels of DAP (R)/frame and DAP (F)/s represent valid parameters for consistent collimation. RESULTS: In 1997, the mean baseline values of DAP for elective CA and PTCA amounted to 37.1 and 31.6 Gy x cm (2), respectively. A reduction of mean fluoroscopy times from 264 to 126 seconds for CA and from 630 to 449 seconds for PCI, both resulted in an overall DAP-reduction of merely 20 %. Optimization of mean radiographic frames from 543 to 98 for CA and from 245 to 142 for PTCA enabled reductions of 53 and 13 %, respectively. By restriction to adequate instead of best-possible image quality for coronary angiography in clinical routine, we achieved an optimized radiographic DAP/frame of 30.3 to 13.3 mGy x cm (2), which enabled a 45 % reduction of overall DAP. Most efficient however was a consistent collimation to the ROI, which resulted in a remarkable radiation reduction by 46 % for CA and by 65 % for PTCA. CONCLUSIONS: Radiation-reducing educational efforts in the clinical routine of invasive cardiology should -- against widely held opinion -- focus less exclusively toward a reduction of fluoroscopy time but more efficiently toward consistent collimation to the region of interest, reduction of radiographic frames and restriction to an adequate instead of best-possible image quality.

[Personal operator dose in invasive cardiology as a function of body height and tube angulation]. / Höhe und Röhrenangulation als die Determinanten der möglichen Untersucher-Ortsdosisleistung in der invasiven Kardiologie.

PURPOSE: To map in an experimental setting of the local personal operator dose for 55 selected tube angulations as a function of body height above ground. MATERIALS AND METHODS: On an Alderson-Rando phantom representing the patient, we performed measurements of fluoroscopy scatter radiation ( micro Sv/h) at the operator's position, for the range of 20 - 200 cm body height, for all tube angulations in 30 degrees steps from right anterior oblique (RAO) 90 degrees to left anterior oblique (LAO) 90 degrees position, and for planes angulated cranially (+) and caudally (-) by 10 degrees, 20 degrees, 30 degrees, and 40 degrees, unless rendered unfeasible by geometric circumstances. RESULTS: Radiation exposure to the operator is lowest between postero-anterior (PA) 0 degrees and RAO 30 degrees angulation, and continuously increases by a factor of approx. 2 towards steep RAO, and to factors of 5 - 10 towards steep LAO views. Craniocaudal angulation at 30 degrees likewise generates personal dose levels 2 - 3 times as high. For all body heights and all LAO tube angulations, the corridor between 0 degrees - 10 degrees caudal angulation generates the least personal scatter dose, likewise irrespective of body height and craniocaudal tube angulations, the corridor between 0 degrees PA - 30 degrees RAO angulation. RAO angulations, however, being inverse to the respective 90 degrees LAO angulations, are generally 4 to 5 times less radiation extensive. Peak levels of the local personal dose vary from 160 cm body height for steep cranial LAO 90 degrees /30 degrees + views (3,500 microSv/h), to 50 cm for cranial PA 0 degrees /30 degrees + (400 micro Sv/h), and to > or = 170 cm (600 micro Sv/h) and < or = 40 cm (300 microSv/h) for steep cranial RAO 90 degrees /30 degrees + views. Caudal angulations generate slightly lower doses, with peak levels at 120 cm for LAO 90 degrees /30 degrees - views (3,000 microSv/h), at 50 cm for PA 0 degrees /30 degrees - views (300 micro Sv/h), and above 170 cm (900 micro Sv/h) and below 40 cm (500 microSv/h) for steep caudal RAO 90 degrees /30 degrees - views. CONCLUSION: The present experimental study on scatter radiation to the operator, as a function of body height and tube angulation, offers a representative data tool for all interventionists for use in invasive cardiology, to confirm the radiation safety of their favored coronary views, or to encourage less radiation-intensive angulations. Moreover, it provides new knowledge about special risks for crucial body regions and enables effective radiation protection strategies.

Effect of atorvastatin on lipid parameters, LDL subtype distribution, hemorrheological parameters and adhesion molecule concentrations in patients with hypertriglyceridemia.

BACKGROUND AND AIM: Hypertriglyceridemia is a risk factor for atherosclerosis that is typically associated with high concentrations of adhesion molecules, impaired hemorrheology and an unfavourable low-density lipoprotein (LDL) subtype distribution. We hypothesised that some of these risk markers might be beneficially influenced by lipid-lowering therapy with atorvastatin in hypertriglyceridemic patients. METHODS AND RESULTS: Nineteen patents with primary hypertriglyceridemia were given 10 mg of atorvastatin per day for four weeks. Their cholesterol, triglyceride, LDL and high-density lipoprotein cholesterol (HDL-C) levels, LDL subtype profile, hemorrheological parameters and E-selectin, vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 concentrations were measured before and at the end of atorvastatin therapy. The levels of total and LDL cholesterol respectively decreased by 25% and 24% (both p < 0.001). Furthermore, cholesterol was reduced by 8-29% in all seven LDL subfractions (density range: 1.020-1.066 g/mL) (p < 0.05). The reduction in triglyceride concentrations was of marginal significance (9%, p = 0.1), but its degree positively correlated with the reduction of small-dense LDL (r = 0.5, p < 0.025). Plasma viscosity and blood viscosity at low shear rates were respectively reduced by 2% and 16% (both p < 0.05). The effect of the treatment on the concentrations of HDL-C, fibrinogen and adhesion molecules was not significant. CONCLUSIONS: Atorvastatin (10 mg/day) not only reduced the plasma concentrations of atherogenic lipoproteins but also improved the LDL-subtype profile and reduced plasma and blood viscosity in patients with hypertriglyceridemia; however, it failed to significantly lower triglyceride concentrations.

Newly synthesized cholesterol in human bile and plasma: quantitation by mass isotopomer distribution analysis.

The purpose of this study was to quantitate the contribution of newly synthesized cholesterol to bile and plasma in humans. Eight healthy volunteers were intravenously infused with 0.125 mmol of [1-(13)C]acetate per kilogram per hour for 15 h. During continuous enteral nutrition, plasma aliquots and samples of duodenal bile were collected hourly. The trimethysilylether of unesterified cholesterol was analyzed by gas chromatography-mass spectrometry for quantitation of the mass fragments M(+0) [mass-to-charge ratio (m/z) 368], M(+1) (m/z 369), M(+2) (m/z 370), M(+3) (m/z 371), and M(+4) (m/z 372). The fractional syntheses of plasma and biliary cholesterol were determined using mass isotopomer distribution analysis. After 6 h of infusion, the 13C enrichment of the acetate pool remained constant at 12%. The fractional synthesis increased continuously during [13C]acetate infusion and reached 4.2% and 5.3% in cholesterol of plasma and bile, respectively. Both were highly correlated, but the fractional synthesis of biliary cholesterol exceeded that of plasma (P < 0.05). It may be concluded that the contribution of de novo cholesterol synthesis to bile exceeds that to plasma but is minor in humans.

The contribution of newly synthesized cholesterol to biliary cholesterol in healthy humans.

Hypersecretion of biliary cholesterol appears to be the key defect in the pathogenesis of cholesterol gallstones, and this may be due to an enhanced synthesis of cholesterol. To measure fractional syntheses of biliary and plasma cholesterol, five male and 3 female healthy humans with an intact enterohepatic circulation were infused intravenously with [1-13C]acetate for 15 h. Samples of duodenal bile and blood were taken hourly and an enteral formula diet was given. Free cholesterol mass distribution was analyzed by gas chromatography mass spectrometry. The Mass Isotopomer Distribution Analysis (MIDA) technique allowed to calculate fractional synthesis. After 6 hours of infusion, the [13C]label of the cytosolic acetate pool reached a plateau of approximately 12%. Individual fractional cholesterol synthesis is plasma and bile correlated significantly (6-15 h) and amounted to 4.2% and 5.3% after 15 h, respectively. It may be concluded from this study, that newly synthesized cholesterol is secreted into bile to a higher extent than into plasma.

Feedback regulation of bile acid synthesis measured by stable isotope kinetics in humans.

OBJECTIVE: To investigate the effect of a low dose of exogenous bile acids and a non-absorbable antibiotic on bile acid kinetics in healthy human subjects. METHODS: Pool size, synthesis rate and fractional turnover rate of the three main bile acids were determined simultaneously with stable isotope labelled bile acids in volunteers before and during intake of 500 mg cholic acid (n = 6), chenodeoxycholic acid (n = 6) or deoxycholic acid (n = 5) per day for 4 weeks or 1 g of paromomycin (n = 6) per day for 2 weeks. RESULTS: Administration of cholic acid nearly doubled the input and pool of deoxycholic acid; chenodeoxycholic acid synthesis was inhibited by 38% and pool size was reduced by 50%. Deoxycholic acid administration resulted in a suppression of both cholic acid and chenodeoxycholic acid synthesis by 53%; the corresponding pool sizes were reduced by 64% and 57%, respectively. The degree of suppression of chenodeoxycholic acid synthesis correlated significantly (P < 0.001) with the relative change of deoxycholic acid input and pool size. Oral chenodeoxycholic acid resulted in an inhibition of cholic acid synthesis (65%) and deoxycholic acid input (67%). The effects of the antibiotic were variable. CONCLUSION: The suppressive effect of cholic acid may be mediated by deoxycholic acid, which is nearly as effective as chenodeoxycholate.