Can phosphorus limitation contribute to the maintenance of sex? A test of a key assumption.

Why sex is so common remains unclear; what is certain is that the predominance of sex despite its profound costs means that it must confer major advantages. Here, we use elemental and nucleic acid assays to evaluate a key element of a novel, integrative hypothesis considering whether sex might be favoured because of differences in body composition between sexuals and asexuals. We found that asexual Potamopyrgus antipodarum, a New Zealand snail, have markedly higher bodily phosphorus and nucleic acid content per unit mass than sexual counterparts. These differences coincide with and are almost certainly linked to the higher ploidy of the asexuals. Our results are the first documented body composition differences between sexual and asexual organisms, and the first detected phenotypic difference between sexual and asexual P. antipodarum, an important natural model system for the study of the maintenance of sex. These findings also verify a central component of our hypothesis that competition between diploid sexuals and polyploid asexuals could be influenced by phosphorus availability.

The validation of fractional flow reserve in patients with coronary multivessel disease: a comparison with SPECT and contrast-enhanced dobutamine stress echocardiography.

UNLABELLED: Fractional flow reserve (FFR) is a new but well established parameter for the hemodynamic evaluation of coronary stenoses. A FFR below 0.75 was validated as functionally significant in coronary one or two vessel disease. This study was designed to prospectively define the best FFR cut off value (BCV) in patients with multivessel disease using two noninvasive tests, myocardial perfusion scintigraphy (SPECT) and contrast-enhanced dobutamine stress echocardiography (DSE) as reference methods. METHODS: 47 symptomatic patients (29 male, mean age 64+/-10 yrs) with angiographically intermediate coronary lesions (50-75% diameter stenosis) entered the study. DSE (5-40 microg/min/kg dobutamine) was performed after intravenous injection of a second generation transpulmonary contrast agent. SPECT (Tc-99m-MIBI) was done at peak stress. All tests (DSE, SPECT and FFR) were performed within 4 weeks. RESULTS: SPECT yielded positive results in 15 and DSE in 16 patients, respectively. Mean FFR measured in the target lesion (RCA n=10; LAD n=22, RCX n=15) was 0.80+/-0.13. FFR was <0.75 in 15 patients. By performing a ROC analysis the BCV (highest sum of sensitivity and specificity) was found at 0.75. At this cut off value using both non-invasive tests as reference method, sensitivity and specificity were 83 and 77%. CONCLUSION: In patients with multivessel disease, a FFR <0.75 identifies a hemodynamically relevant lesion as compared to DSE and SPECT. This study underlines that FFR criteria are also applicable in patients with complex coronary artery disease.

Early time course of neointima formation and vascular remodelling following percutaneous coronary intervention and vascular brachytherapy of in-stent restenotic lesions as assessed by intravascular ultrasound analysis.

In-stent restenosis (ISR) represents the major limitation of stent implantation. Treatment, although of relative technical ease, is unsatisfactory due to a high incidence of recurrent restenosis. Vascular brachytherapy (VBT) has emerged as a powerful adjunct therapeutic modality to treat ISR. Inhibition of neointima formation has been regarded as the relevant mechanism of action. Yet, positive remodelling has been suspected as another contributing factor. Since only very few precise analyses of the extent, distribution and time course of the respective mechanims exist, the goal of the present study was to describe the changes of the vessel geometry at the target lesion and at the reference site following angioplasty and VBT of ISR in 42 patients by means of quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) before and after the index procedure and at the 3 and 6 month follow-up. By QCA the acute lumen gain measured 2.2+/-0.8 mm, the late lumen loss at 3 months was 0.1+/-0.5 mm and at 6 months 0.4+/-0.7 mm. By IVUS luminal cross-sectional area increased from 1.5+/-1.2 mm(2) to 7.9+/-1.9 mm(2) (p<0.001). The intima hyperplasia cross-sectional area at 3 months was only 0.2+/-1.0 mm(2) (p=0.191), but increased to 0.7+/-0.6 mm(2) (p<0.001) at 6 months resulting in a lumen cross-sectional area of 7.1+/-1.7 mm(2). Stent dimensions did not show any significant changes over time. The external elastic membrane cross-sectional area at 3 months increased by 1.3+/-1.9 mm(2) (p<0.001), and showed a further increase by 0.7+/-2.9 mm(2) at 6 months. Positive remodelling could be demonstrated also at the reference segment. In conclusion the absolute amount of intima hyperplasia during a 6-month follow-up period after VBT of ISR is low and most pronounced between the third and sixth month. Besides this, predominantly within the first 3 months of follow-up, significant positive remodelling could be demonstrated at the target lesion and at the reference site. Both observed effects may contribute to the preservation of the vessel lumen.

Fractional flow reserve for the prediction of cardiac events after coronary stent implantation: results of a multivariate analysis.

OBJECTIVE: To determine the prognostic value of fractional flow reserve (FFR) measurements after coronary stent implantation including multiple clinical and angiographic parameters collected in one centre. METHODS: 119 consecutive patients were enrolled who had a stent implanted with the use of a pressure wire as a guidewire. Patients were followed up for at least six months. Any death, myocardial infarction, and target vessel revascularisation were considered major adverse cardiac events (MACE). Multivariate logistic regression was used to determine adjusted odds ratios (OR) and 95% confidence intervals (CI) for FFR and covariates. RESULTS: Complete follow up data were available for all 119 patients. Pre-interventional FFR increased from 0.65 (0.15) to 0.94 (0.06) (p < 0.0001) after stent implantation. Eighteen MACE (15%) occurred during follow up including 15 (12.6%) target vessel revascularisations. Final FFR was significantly higher in patients without than in patients with an event (0.95 (0.05) v 0.88 (0.08), p = 0.001). In the multivariate logistic regression analysis, only final FFR < 0.95 (OR 6.22, 95% CI 1.79 to 21.62, p = 0.004) and reduced left ventricular function (OR 0.95, 95% CI 092 to 0.99, p = 0.021) remained as significant independent predictors for MACE. CONCLUSION: These results including multiple parameters underline that FFR after coronary stenting is a strong and independent predictor for subsequent cardiac events after six months' follow up.

[Effect of immunosuppression-induced hypogonadism on bone metabolism after heart transplantation]. / Einfluss des Immunsuppressiva-induzierten Hypogonadismus auf den Knochenmetabolismus nach Herztransplantation.

BACKGROUND AND OBJECTIVE: Accelerated bone loss is a well recognized complication after cardiac transplantation (HTx). The role of an immunosuppressive-induced hypogonadism, a well-known cause of osteoporosis in men and its prevention are less defined after HTx. The aim of this study was first, to evaluate the incidence of hypogonadism after HTx and its influence on bone mineral metabolism and second, to assess the effect of a testosterone replacement therapy in hypogonadal transplants. PATIENTS AND METHODS: Due to hormonal status, 88 male cardiac transplants were randomised to a normogonadal or hypogonadal group. At baseline as well as after 1 and 2 years bone mineral density (BMD g/cm (2), T-score) was measured at the lumbar spine with DEXA. All patients received a basic therapy of calcium and vitamin D. The hypogonadal patients received additional testosterone. RESULTS: 21 patients (24 %) showed an age-independent hypogonadism. Hypogonadal transplants showed a significant lower BMD (p < 0.001) (BMD = 0.8070 g/cm (2), T-value = -2.6514) than normogonadal patients (BMD = 0.9882 g/cm (2), T-value = -1.0568). Despite testosterone replacement hypogonadal patients showed no significant additional increase in BMD over 1 - 2 years compared with the normogonadal. CONCLUSION: Male cardiac transplants in all age groups show an high prevalence of hypogonadism (approximately 25 %) which contributes to a significant bone loss. An additional testosterone substitution did not significantly increase BMD.

Comparison of pressure measurement, dobutamine contrast stress echocardiography and SPECT for the evaluation of intermediate coronary stenoses. The COMPRESS trial.

BACKGROUND: DSE and SPECT are two well-established methods to non-invasively investigate the functional significance of coronary artery stenoses in patients with coronary artery disease. The measurement of Fractional Flow Reserve has emerged a new invasive reference standard for lesion specific quantification of coronary artery stenoses. The objective of our prospective study was to compare sensitivity and specificity of Dobutamine Stress Echocardiography (DSE) and Single Photon Emission Computer tomography (SPECT) with the pressure derived Fractional Flow Reserve (FFR) for the identification of hemodynamic relevant coronary lesions in patients with predominately coronary multivessel disease and angiographically intermediate stenoses. METHODS: Inclusion criteria were a coronary lesion of 50-75% diameter stenosis by visual assessment in patients with known or suspected CAD. SPECT, DSE and FFR testing was performed within one week of coronary angiography. RESULTS: The study comprised 48 consecutive symptomatic patients. In 41 cases, a coronary multivessel disease was present. Mean FFR was 0.80 +/- 0.13 (0.41-1.0). Overall sensitivity of DSE and SPECT was 67% and 69% whereas specificity reached 77% and 87%. However, sensitivity was significantly reduced if the target lesion was located distally. DSE showed poor results if the lesions were located in the circumflex artery or if a history of prior myocardial infarctions was present. CONCLUSION: DSE and SPECT are both useful methods for the non-invasive assessment of coronary artery disease. DSE showed reasonable combination of sensitivity and specificity even in patients with multivessel disease. Although use of noninvasive stress tests is only limited in patients with prior myocardial infarctions and invasive stress testing should be preferred in these patients.

A randomized comparison of 4 doses of intracoronary adenosine in the assessment of fractional flow reserve.

BACKGROUND: Fractional flow reserve (FFR) is a measure of coronary stenosis severity that is based on pressure measurements obtained at maximal hyperemia. Therefore, achievement of maximal vasodilatation of the coronary microcirculation is a prerequisite for the measurement of FFR. The study was designed to address the hypothesis that intracoronary adenosine yields more complete vasodilatation of the coronary microcirculation when high doses are used, resulting in a more accurate FFR measurement. METHODS: Thirty-six patients with 43 moderate lesions underwent determination of FFR during cardiac catheterization. FFR was calculated in all lesions as the ratio of the distal coronary pressure to the aortic pressure at hyperemia. Different incremental doses of intracoronary adenosine (16, 24, 32 and 40 microg for both coronary arteries) were administered in a randomized fashion. RESULTS: No adverse events occurred with any intracoronary adenosine bolus. At baseline there were no significant differences for mean aortic and distal coronary pressure, heart rate as well as FFR values between the different doses. FFR was not significantly altered from the different incremental adenosine doses. However, in 27 (63%) out of 43 lesions there was a further reduction of FFR up to 0.23 when a dose >16 microg was injected. CONCLUSIONS: This study suggests that doses of adenosine up to 40 microg are safe and can be used to achieve a more pronounced vasodilatation in individual patients compared to the standard doses. This may have therapeutic impact with FFR values near cut-off points in patients undergoing diagnostic coronary angiography as well as in patients in whom FFR is used to assess the outcome of interventions.

[Clinical and angiographic one-year follow-up of vascular beta-brachytherapy for coronary lesions treated by a stent with a very high risk for restenosis]. / Klinischer und angiographischer Ein-Jahres-Verlauf nach vaskulärer Beta-Brachytherapie von Instent-Restenosen mit sehr hohem Rezidivrisiko.

BACKGROUND: Vascular brachytherapy (VBT) has been proven to reduce restenosis rate and unwanted cardiac events in several randomized trials. Long-term data on populations at high risk for re-interventions are few. The aim of this study was to assess the acute and one-year outcome of beta-radiation in coronary in-stent restenoses with a high likelihood of recurrence. METHODS: In 79 patients, VBT using 90Yttrium/Strontium or 32Phosphorus, was performed. Clinical and angiographic follow-up was carried out after 6 months and 1 year. RESULTS: 44.4 % of patients had three-vessel coronary artery disease and a high prevalence of cardiovascular risk factors and comorbidity. Mean lesion length was 36.8+/-18.9 mm. VBT was successful in all patients. Fractionation of VBT was necessary in 2,5 %. Acute gain of luminal diameter was 2.15+/-0.89 mm. During the hospital stay one acute myocardial infarction (AMI) not associated with VBT occurred. After 6 months loss of luminal diameter measured 0.39+/-0.47 mm, equaling a restenosis rate (RR) of 16.8 % (1 year: 0.60+/-0.56 mm, RR 33.5 %). 18.9 % of patients required revascularization of the target lesion (1 year: 29.5 %). After 6 months, all patients survived, three had an AMI after discontinuation of clopidogrel, one of them was asymptomatic (1 year: 1 cardiac death, 2 symptomatic AMI). CONCLUSION: Beta-VBT in patients at a high risk for recurrence after angioplasty is feasible and safe. Though the clinical and angiographic results at 1 year showed some impairment as opposed to the 6-months-follow-up, they nevertheless are largely superior to those patients from historic controls not treated with VBT.

[Edge effect and late thrombosis -- inevitable complications of vascular brachytherapy?]. / Edge effect und späte Thrombose -- Notwendiges Ubel oder vermeidbare Nebenwirkung der intrakoronaren Brachytherapie?

Restenosis is the limiting entity after percutaneous coronary angioplasty. Vascular brachytherapy for the treatment of in-stent restenosis has been shown to reduce the repeat restenosis rate and the incidence of major adverse events in several randomized trials. Besides the beneficial effects, brachytherapy yielded some unwanted side effects. The development of new stenoses at the edges of the target lesion treated with radiation is termed edge effect. It occurs after afterloading brachytherapy as well as after implantation of radioactive stents. It is characterized by extensive intimal hyperplasia and negative remodeling. As contributing factors the axial dose fall-off, inherent to all radioactive sources, and the application of vessel wall trauma by angioplasty have been identified. The combination of both factors, by insufficient overlap of the radiation length over the injured vessel segment, has been referred to as geographic miss. It has been shown to be associated with a very high incidence of the edge effect. Avoidance of geographic miss is strongly recommended in vascular brachytherapy procedures. Late thrombosis after vascular brachytherapy is of multifactorial origin. It comprises platelet recruitment, fibrin deposition, disturbed vasomotion, non-healing dissection and stent malapposition predisposing to turbulent blood flow. The strongest predictors for late thrombosis are premature discontinuation of antiplatelet therapy and implantation of new stents during the brachytherapy procedure. With a consequent and prolonged antiplatelet therapy, the incidence of late thrombosis has been reduced to placebo levels. Edge effect and late thrombosis represent unwanted side effects of vascular brachytherapy. By means of a thorough treatment planning and prolonged antiplatelet therapy their incidences can be largely reduced. With regard to the very favorable net effect, they do not constitute relevant limitations of vascular brachytherapy.

[Coronary interventions in old patients presenting with cardiogenic shock]. / Kathetergestützte Revaskularisation bei einer alten Patientin im kardiogenen Schock.

HISTORY AND CLINICAL FINDINGS: A 80-year-old unconscious woman was admitted to our hospital. She had suffered from angina pectoris and progressive dyspnea for three days. She had been in pulmonary edema 6 months ago. Clinical examination revealed low blood pressure of 90/60 mmHg, central cyanosis and signs of pulmonary congestion. INVESTIGATIONS: Laboratory findings comprised elevated creatinkinase, troponin and lactate dehydrogenase as well as reduced sodium. CLINICAL COURSE: After intubation and mechanical ventilation the patient underwent cardiac catheterization because of the cardiogenic shock. Coronary angiography revealed severe coronary artery disease with high grade stenoses of the right coronary artery and of the main stem of the left coronary artery. After initiating intraaortic balloon counterpulsation, transcatheter revascularization of the right and left coronary artery was performed, leading to an improvement of the systolic left ventricular function. But the patient finally died due to cardiac pump failure. CONCLUSION: Elderly patients presenting with cardiogenic shock and additional risk factors have the highest mortality. Thus the decision for cardiac catheterization and eventual intervention should be made on a case-by-case basis. Successful angioplasty may reduce mortality by approximately 20 %. Due to the usually severe comorbidity absolute mortality is nevertheless very high.

[Intravascular ultrasound guided directional atherectomy and stent implantation of an unprotected main stem in a heart transplant patient with comorbidity]. / IVUS-geführte direktionale Atherektomie und Stentimplantation des ungeschützten Hauptstammes eines multimorbiden herztransplantierten Patienten.

Following orthotopic heart transplantation (HTx), development of transplant vasculopathy (TVP) is the limiting medical entity leading to significant morbidity and mortality beyond the first year after HTx. Selection of a suitable strategy for repeat revascularisation--transcatheter angioplasty, coronary artery bypass grafting or repeat HTx--depends on various parameters including coronary morphology, left ventricular performance, comorbidity, availability of graft material and donor organs. Catheter-based interventions on the main stem of the left coronary artery are feasible, but a relatively lower primary success rate and a higher complication rate and significantly increased mortality have to be expected. We report on a patient who underwent HTx 9 years ago and developed severe transplant vasculopathy revealing significant main stem stenosis, making reintervention necessary. Due to age, coronary artery morphology and comorbidity the patient was not considered for coronary artery bypass grafting or repeat HTx. We performed successful IVUS-guided directional coronary atherectomy and stent implantation on a distal stenosis of the unprotected main stem. Our case demonstrates a predictable procedural risk and favourable primary result of left main stem angioplasty procedures, thus providing a therapeutic option for patients who are poor candidates for operative revascularisation strategies.

Vascular brachytherapy for treatment of cardiac allograft vasculopathy.

A high restenosis rate often follows treatment of coronary stenoses in cardiac allograft vasculopathy. We report successful coronary brachytherapy of a second in-stent restenosis in a patient after heart transplantation.

Serial intravascular ultrasound and quantitative coronary angiography after self-expandable wallstent coronary artery implantation.

Serial intracoronary ultrasound studies revealed significant postprocedural stent expansion accompanied by significant stent shortening during long-term follow-up. The disadvantageous lumen loss by neointimal formation could be balanced by late stent expansion.

Transpulmonary contrast echocardiography: effects on delineation of endocardial border, assessment of wall motion and interobserver variability in stress echocardiograms of limited image quality.

BACKGROUND: A major limitation of stress echocardiography remains poor image quality. OBJECTIVE: To investigate the effects of transpulmonary contrast echocardiography (TCE) with BY 963 on endocardial border delineation, detectability of wall motion abnormalities and interobserver variability at rest and during dobutamine stress echocardiography (DSE) in subjects with technically limited baseline echocardiograms. METHODS: BY 963 was administered intravenously to 36 patients (5 ml for parasternal LAX/SAX, 10 ml for apical four-chamber/two-chamber view) both at rest and at peak stress during DSE. Two observers applied a delineation score (0, endocardial border not visible; 1 border poorly visible; and 2, border clearly visible) to 12 wall segments in the parasternal and 10 in the apical views both before and after administration of BY 963. A 16-segment wall-motion score was used. RESULTS: In parasternal views, the delineation score was not improved by TCE. In the apical views, TCE significantly increased the delineation score (from 14.1 +/- 5.4 to 20.7 +/- 4.2 at rest and from 14.6 +/- 5.7 to 21.7 +/- 4.1 under stress, both P< 0.01). For 18 of 25 patients with coronary artery disease (> or = 70% stenosis) results of DSE were positive before TCE, whereas results were positive for 21 patients during TCE. For 10 of 11 patients without coronary artery disease, results of DSE were negative both before and during TCE. For the apical delineation score, interobserver variability was decreased significantly by TCE (from 19.5 +/- 19.6 to 8.2 +/- 15.6% at rest and from 20.2 +/- 19.6 to 3.3 +/- 11.4% at peak stress, both P< 0.01). CONCLUSIONS: TCE enhances endocardial border delineation in apical views at rest and during DSE, resulting in a decrease of interobserver variability and an improvement in assessment of wall motion. Use of TCE, at least how it was applied in this investigation, seems not to be indicated for parasternal projections.

Progression of cardiac allograft vascular disease as assessed by serial intravascular ultrasound: correlation to immunological and non-immunological risk factors.

OBJECTIVE: To characterise the severity and progression of cardiac allograft vascular disease (CAVD) in a large patient cohort, and to evaluate possible immunological and non-immunological risk factors for progression. DESIGN: A prospective observational study using intravascular ultrasound. SETTING: Two university hospitals. PATIENTS AND MAIN OUTCOME MEASURES: Changes in focal plaque, lumen, and total vessel area (worst site method) were assessed at baseline and after 12.1 (2.8) months (mean (SD)) of follow up in a cohort of 96 patients (79 male, 17 female; mean age 48.7 (9.6) years; time post-transplant 26.0 (32.4) months). RESULTS: Overall, the mean (SD) intimal index of worst sites increased by 6.7 (8.8)%. The increase in the first 12 months was 7.5 (9.4)%, v 5.9 (8.0)% after the first year (NS). Analysing immunological and non-immunological risk factors (age, underlying disease, sex, donor age, immunosuppression, cytomegalovirus, rejection episodes, cholesterol), low density lipoprotein (LDL) cholesterol was found to be the most important predictor of severe progression (as defined by an increase in intimal index of >/= 15% (p = 0.01). CONCLUSIONS: Progression of CAVD is characterised by a continuing increase in intimal hyperplasia, especially within the first year after heart transplantation. LDL cholesterol is an important predictor of major progression.

Cyclosporine versus tacrolimus (FK 506) for prevention of cardiac allograft vasculopathy.

This study prospectively compared the impact of cyclosporine A and tacrolimus on the development of cardiac allograft vasculopathy. By using serial intravascular ultrasound examinations, a trend toward a more pronounced progression was noted in the tacrolimus group in the first year after heart transplantation.