Cardiac biomarkers for risk stratification of arrhythmic death in patients with heart failure and reduced ejection fraction.

Objectives. Patients with heart failure and reduced left ventricular ejection fraction (HFrEF) are prone to ventricular tachyarrhythmias. We tested whether biomarkers C-terminal Endothelin 1 (CT-ET1), midregional pro atrial natriuretic peptide (MR-proANP) and midregional pro adrenomedullin (MR-proADM) might improve risk stratification for arrhythmic death.Methods: This prospective observational study included 160 heart failure patients with ischaemic cardiomyopathy (ICM) or non-ischaemic, dilated cardiomyopathy (DCM) and 30 control patients without heart disease. Primary endpoint was arrhythmic death (ArD) or resuscitated cardiac arrest (resCA).Results: A total of 61 patients died during the median follow-up of 7.0 [5.2-8.4] years. An ArD or resCA was observed in 48 patients. Plasma levels of CT-ET1 (p = 0.002), MR-proANP (p < 0.001) and MR-proADM (p = 0.013) were significantly higher in ICM or DCM patients compared to controls. MR-proANP levels in ICM patients were associated with a significantly increased risk for ArD or resCA (hazard ratio (HR) = 1.42, [95%CI: 1.08-1.85], p = 0.011) in a multivariable Cox regression model. Plasma levels of CT-ET1 (HR = 1.07 [0.98-1.17], p = 0.113) and MR-proADM (HR = 1.80 [0.92-3.55], p = 0.087) were not associated with ArD or resCA in ICM patients. No significant association with ArD or resCA was found in DCM patients. Multivariable Cox regression showed that CT-ET1 (HR = 1.14 [1.07-1.22], p < 0.001), MR-proANP (HR = 1.64 [1.29-2.08], p < 0.001) and MR-pro ADM (HR = 2.06 [1.12-3.77], p = 0.020) were associated with a higher risk for overall mortality.Conclusion: Patients with HFrEF had elevated levels of CT-ET1, MR-proANP and MR-proADM. Plasma levels of MR-proANP are useful as predictor for arrhythmic death in patients with ICM.

Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL), an acute phase protein released by neutrophils, has been described as biomarker of inflammatory states. Type 2 diabetes mellitus (T2DM) is characterized by increased inflammation and an elevated risk for embolization of carotid artery stenosis (CAS). We aimed to explore the role of NGAL systemically and in plaques of diabetics undergoing carotid endarterectomy. Moreover, the potential anti-inflammatory effect of metformin on NGAL was addressed in diabetics. METHODS: Serum NGAL and matrix metalloproteinase (MMP)-9/NGAL levels were measured in 136 patients (67 with T2DM vs. 69 non-diabetics) by specific ELISA. Endarterectomy samples were graded histologically according to the American Heart Association´s classification. NGAL mRNA expression was detected using RealTime-PCR in carotid endarterectomy specimens. RESULTS: Serum NGAL [median 107.4 ng/ml (quartiles: 75.2-145.0) vs. 64.4 (50.4 -81.3), p < 0.0001] and MMP-9/NGAL [41.5 ng/ml (20.8-63.9) vs. 27.6 (16.0-42.4), p = 0.017] were significantly elevated in diabetics compared to non-diabetics, as were leukocytes, neutrophils, C-reactive protein and fibrinogen (all p < 0.05). In patients with symptomatic and asymptomatic CAS diabetics had higher NGAL levels compared to non-diabetics [128.8 ng/ml (100.8-195.6) vs. 64.8 (48.9-82.2] and [101.6 ng/ml (70.1-125.3) vs. 63.8 (51.0-81.3), respectively, both p < 0.0001]. Presence of T2DM and type VI plaques (with surface defect, hemorrhage or thrombus) had a profound impact on NGAL levels (both p < 0.01) in multiple linear regression analysis. NGAL mRNA was detectable in 95% of analyzed carotid artery lesions of diabetics compared to 5% of non-diabetics (p < 0.0001). Accordingly, cerebral embolization was more frequent in diabetics (52.2% vs. 29%, p = 0.006). Metformin treatment was associated with decreased NGAL [60.7 ng/ml (51.9-69.2) vs. 121.7 (103.7-169.9), p < 0.0001] and MMP-9/NGAL [20.8 ng/ml (12.1-26.5) vs. 53.7 (27.4-73.4), p = 0.007] in diabetics and reduced leukocyte infiltration in carotid lesions of diabetics. CONCLUSIONS: Higher NGAL levels in serum and plaques are associated with T2DM in patients with CAS. Metformin significantly reduced the inflammatory burden including NGAL in diabetics. Early treatment of these patients may be recommended, as elevated NGAL levels were linked with vulnerable plaques prone for embolization.

Neutrophil Gelatinase-Associated Lipocalin (NGAL) is Associated with Symptomatic Carotid Atherosclerosis and Drives Pro-inflammatory State In Vitro.

OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL), a protein found in activated neutrophils, is expressed in kidney tubule cells in response to noxious stimuli, and is thus recognized as a marker of acute kidney injury. Recent studies have suggested that NGAL could also have pathophysiological importance in cardiovascular diseases. The aim of the present study was to examine NGAL expression in human carotid endarterectomy tissues ex vivo as well as the effects of NGAL in the main cell types involved in atherogenesis, namely in human macrophages, endothelial cells, and smooth muscle cells in vitro. METHODS: NGAL protein was analyzed in human endarterectomy samples from patients with asymptomatic and symptomatic carotid stenosis by immunofluorescence, and NGAL mRNA expression was detected using RealTime-PCR. Human monocyte derived macrophages (MDM), human coronary artery smooth muscle cells (HCASMC), and human umbilical vein endothelial cells (HUVEC) were treated with recombinant human (rh) NGAL at different concentrations. Interleukin (IL)-6, IL-8, and monocyte chemo-attractant protein-1 (MCP-1) were determined by specific enzyme linked immunosorbent assays (ELISAs) in culture supernatants of such treated cells. RESULTS: Expression of NGAL protein was demonstrated by macrophages, smooth muscle cells, and endothelial cells in human carotid atherosclerotic tissue. NGAL mRNA expression was detected at a higher rate in atherosclerotic tissue of patients with symptomatic carotid stenosis (in 70%; n = 19) compared with asymptomatic patients (in 37%; n = 20, p < .001). Treatment of MDM, HCASMC, and HUVEC with rhNGAL led to a significant (p < 0.05) and concentration dependent increase of pro-inflammatory cytokines IL-6, IL-8, and MCP-1 in all cell types analyzed. CONCLUSION: By induction of pro-inflammatory mediators in human macrophages, smooth muscle cells and endothelial cells, NGAL, which is predominantly expressed in atherosclerotic plaques of symptomatic patients, could be involved in creating the local and systemic pro-inflammatory environment characteristic for atherosclerosis.

Interleukin-33 induces urokinase in human endothelial cells--possible impact on angiogenesis.

BACKGROUND: Urokinase-type plasminogen activator (u-PA) plays a pivotal role in extracellular proteolysis and is thought to be critically involved in the modulation of angiogenesis. Interleukin (IL)-33 is a member of the IL-1 cytokine family, which is thought to act as danger signal that is released from cells after injury. IL-33 is involved in the pathogenesis of various inflammatory diseases and previously was shown to induce angiogenesis and inflammatory activation of endothelial cells. OBJECTIVE: We investigated the impact of IL-33 on u-PA in endothelial cells as a new possible function for IL-33. METHODS AND RESULTS: We could demonstrate that IL-33 upregulated u-PA mRNA expression and protein production in human coronary artery and human umbilical vein endothelial cells in a time- and concentration-dependent manner via interaction with its receptor ST2 and activation of the nuclear factor-κB pathway but independent of autocrine IL-1-induced effects. The hydroxymethylglutaryl-coenzyme A reductase inhibitor simvastatin abrogated the IL-33-induced increase in u-PA, thus providing further evidence for pleiotropic effects of statins. IL-33 induced u-PA-dependent capillary-like tube formation and vessel sprouting. In human carotid atherosclerotic plaques (n = 16), u-PA mRNA positively correlated with IL-33 mRNA expression (r = 0.780, P < 0.001). Furthermore, IL-33 and u-PA protein were detected in endothelial cells in these samples using fluorescence immunohistochemistry. CONCLUSIONS: We hypothesize that IL-33, representing a danger signal that is released after tissue damage, in addition to its role in the inflammatory activation of endothelial cells, is involved in u-PA-driven angiogenesis, a process that has been shown before to be linked to inflammation in various pathologies.

Systematic review of perianal implants in the treatment of faecal incontinence.

BACKGROUND: Injectable bulking agents have been used with varying success for the treatment of faecal incontinence. This systematic review aimed to investigate the various injectable agents and techniques used for the treatment of faecal incontinence, and to assess their safety and efficacy. METHODS: Thirty-nine publications were identified and studied. The following variables were pooled for univariable analysis: type, location, route of bulking agents, and the use of ultrasound guidance, antibiotics, laxatives and anaesthetics. Predictors of the development of complications and successful outcomes were identified by multivariable logistic regression analysis. RESULTS: A total of 1070 patients were included in the analysis. On multivariable analysis, the only significant predictor of the development of complications was the route of injection of bulking agents (odds ratio 3·40, 95 per cent confidence interval 1·62 to 7·12; P = 0·001). Two variables were significant predictors of a successful short-term outcome: the use of either PTQ(®) (OR 5·93, 2·21 to 16·12; P = 0·001) or Coaptite(®) (OR 10·74, 1·73 to 65·31; P = 0·001) was associated with a greater likelihood of success. Conversely, the use of local anaesthetic was associated with a lower likelihood of success (OR 0·18, 0·05 to 0·59; P = 0·005). Failure to use laxatives in the postoperative period resulted in a poorer medium- to longer-term outcome (OR 0·13, 0·06 to 0·25; P = 0·001). CONCLUSION: This systematic review has identified variations in the practice of injection of bulking agents that appear to influence the likelihood of complications and affect the outcomes after treatment.

A classification system for faecal incontinence based on anorectal investigations.

BACKGROUND: Faecal incontinence is a socially disabling condition that affects a heterogeneous population of patients. There is no standardization of investigations, and treatment outcomes are variable. The major limitation for comparing the results from different studies is the lack of a pretreatment classification of incontinence. The aim of this study was to review the anorectal investigation findings and propose a simple, repeatable classification for faecal incontinence. METHODS: Patients who had anorectal investigations for defaecatory disorders from February 2000 to September 2006 were analysed retrospectively. All patients had anorectal manometry, anal mucosal electrosensitivity testing and endoanal ultrasonography. RESULTS: Of a total of 1294 patients, 135 were excluded, leaving 1159 (460 continent and 699 incontinent) for analysis. The patients were divided into four groups: traumatic incontinence, neuropathic faecal incontinence, combined faecal incontinence and idiopathic faecal incontinence. The manometric variables and demographics were distinct in these groups. CONCLUSION: Patients with faecal incontinence can be classified into different groups with distinct pathophysiological variables. Such a classification system will enable comparison and interpretation of the outcomes of different studies and also help in the selection of patients for appropriate treatments.

Intra-anal collagen injection for the treatment of faecal incontinence.

BACKGROUND: Intra-anal injectable agents have been used to treat faecal incontinence. The aim of this study was to report the experience of a cohort of patients who underwent intra-anal injection of collagen and to determine which patients benefited from the technique. METHODS: Data, including age, sex, incontinence score, classification of incontinence, baseline resting pressure and vector volume, were collected prospectively for 73 consecutive patients (59 women) undergoing intra-anal collagen injection. Patients were reviewed after treatment and incontinence scores documented. A proportion of patients also underwent repeat anorectal physiological testing 8 weeks after the procedure. RESULTS: At a median follow-up of 12 months after the intra-anal injection, 63 per cent of patients had an improved incontinence score and 73 per cent reported an overall improvement in symptoms. Logistic regression showed that older age and idiopathic faecal incontinence were predictors of a successful outcome (P = 0.042 and P = 0.048 respectively). CONCLUSION: Intra-anal collagen injection appears to have a role in the treatment of faecal incontinence. The majority of patients can expect both objective and subjective improvement. The best results are achieved in older patients and in those with idiopathic incontinence.

Endoscopic laser ablation of advanced rectal carcinoma--a DGH experience.

BACKGROUND: Patients with inoperable advanced rectal carcinoma require palliation for local symptoms. Endoscopic Nd-Yag laser ablation is a valid palliative treatment option in patients with advanced rectal carcinoma who are poor operative risks due to coexistent multiple comorbidities. METHODS: All patients who cannot undergo radical surgery due to various factors such as tumour size, poor risk patients, distant metastasis and refusal to undergo surgery were offered palliation with endoscopic Nd-YAG laser ablation. Indications included troublesome bleeding, local recurrence, mucous discharge and impending obstruction. Patients were admitted on the day of treatment, phosphate enema given for bowel preparation and endoscopic ablation done through a flexible sigmoidoscope under intravenous sedation with midazolam. All patients were discharged the next day after overnight observation. Patients were reviewed every 3 months and laser ablation repeated if deemed necessary. RESULTS: Eleven patients (7 males, 4 females; mean age 83.6 years, range 77-90 years) underwent endoscopic laser ablation in a District General Hospital --8 for rectal carcinoma, 2 for rectosigmoid tumour and 1 for recurrent tubulovillous adenoma. The number of treatment episodes varied from 1 to 12 with symptom free interval from 2 to 18 months between treatment episodes. There were 3 failures, one patient required defunctioning colostomy, one patient was referred for radiotherapy due to persistent symptoms and in one patient laser treatment had to be abandoned due to local extent. There were no immediate post-treatment complications, but one patient developed incontinence after 5 episodes which might be attributable to tumour infiltration. DISCUSSION: Endoscopic laser ablation is a practical and feasible alternative to other palliative treatment modalities in the management of this unfortunate category of patients due to low morbidity and mortality, short hospitalization and low complication rates.

Comparison of rigid vs flexible sigmoidoscopy in detection of significant anorectal lesions.

OBJECTIVE: Sigmoidoscopy is an essential tool in colorectal clinics in the detection of anorectal lesions including rectosigmoid adenomas and carcinomas. However, rigid sigmoidoscope (RS) is still more widely used than flexible sigmoidoscope (FS) as the primary investigation, despite the fact that the latter is more comfortable to the patient and has greater diagnostic yield. Hence we wanted to compare the two modalities in terms of diagnostic use for picking up significant anorectal lesions. METHODS: A retrospective review of all patients referred to the colorectal clinic who had undergone both rigid and flexible sigmoidoscopy for investigation of colorectal symptoms in 2001 was done. Findings recorded during rigid and flexible sigmoidoscopy including depth of insertion, site of lesion and complications were analysed. RESULTS: 152 patients underwent both rigid and flexible sigmoidoscopy as part of investigation of colorectal symptoms. Of the 115 (75.6%) declared normal by RS, 39 (33.9%) had significant lesions including 7 polyps and 4 malignant lesions within 20 cm of the anal verge during FS. Of the 31 patients (20.4%) in whom RS was not helpful due to faecal loading, 15 (48.4%) had significant lesions including 4 malignancies and 1 polyp --all within 20 cm of the anal verge during FS. Only 2 polyps and 1 malignant lesion were picked up by both flexible and rigid sigmoidoscopy. There were no complications in both procedures. CONCLUSION: Since flexible sigmoidoscopy is superior to rigid sigmoidoscopy in terms of patient comfort, diagnostic value and ease of doing procedures like biopsy and polypectomy; it can be used as a front line investigation to exclude colorectal pathology in out patient clinics. The utility of rigid sigmoidoscope is in question and in view of obvious shortcomings, may be replaced by flexible sigmoidoscopy, though obvious resource constraints need to be considered.

Does the need to self-digitate or the presence of a large or nonemptying rectocoele on proctography influence the outcome of transanal rectocoele repair?

INTRODUCTION: Transanal repair of anterior rectocoele is a well described technique with variable success rate. In our department we offer repair to patients who fit the following criteria; the need to self digitate (transvaginal or perineal); a large rectocoele; a nonemptying rectocoele. Using these selection criteria previous authors have shown excellent results. The aim of our study was to review our results using this selective approach and also to determine whether the need to self digitate, the presence of a large rectocoele and the degree of emptying could predict which patients would achieve a successful result. METHODS: Fifty-five patients underwent repair over a three-year period. The main presenting symptom was noted for each patient and also whether self-digitation was required in order to achieve successful evacuation. Dynamic evacuation proctography was performed on all patients. Size of rectocoele, percentage of paste expelled and other proctographic abnormalities were noted for each patient. Follow up was at 6 weeks and 6 months at which point patients were asked whether their symptoms had resolved, improved, remained the same or had worsened. RESULTS: Complete data were available for 48 of the patients (median age 52 years, IQR 43-63). The presenting complaint was constipation in 22 patients, obstructive defaecation in 15, incomplete evacuation in 5, postdefaecation soiling in 4 and dyspareunia in 2. Thirty-eight patients noted the need to self-digitate, 10 did not. Proctography revealed a large rectocoele (> 4 cm) in 22 patients and a medium or small rectocoele (< 4 cm) in 26 patients. There was a rectocoele alone in 34 patients, in combination with perineal descent in 11 and with intussusception in 3. Median percentage of paste expelled was 70% (range 20-95). At 6 weeks postoperatively, 43 patients had complete resolution of their symptoms whilst 5 reported only some or no improvement. At 6 months, 37 patients sustained complete resolution of their symptoms and 11 did not. Pre-operative factors were compared for these two groups of patients. There was no difference in age (P > 0.05, Mann-Whitney U-test) between the two groups There was also no difference in size of rectocoele, degree of emptying, the presence of another proctographic abnormality and the need to self-digitate between the two groups (P > 0.05, Fisher's exact test). DISCUSSION: No factors were seen to distinguish between the successful and unsuccessful groups of patients following rectocoele repair, however, an overall success rate of 75% was achieved using our selection criteria. This figure is in keeping with reported success rates in the literature.

Prognostic value of myocardial viability determined by a 201Tl SPECT study in patients with previous myocardial infarction and mild-to-moderate myocardial dysfunction.

The prognostic meaning of myocardial viability is most important in patients with severe left ventricular dysfunction and ischaemic heart disease, but its prognostic significance in patients with previous myocardial infarction and mild-to-moderate myocardial dysfunction is uncertain. The aim of this study was to assess the prognostic value of a 201Tl single photon emission computed tomography (SPECT) rest-redistribution study in patients with previous myocardial infarction, ischaemic heart disease and mild-to-moderate myocardial dysfunction. Myocardial viability was assessed in 55 patients (50 male; mean age 58+/-9 years) by 201Tl SPECT rest-redistribution (after 4 h) scintigraphy. All patients had previous myocardial infarction (>3 months) and angiographically documented coronary artery disease, with the mean ejection fraction of 43+/-10%. Out of 55 patients, 20 were medically treated and 35 were revascularized. The follow-up period for adverse cardiac events, including death and non-fatal myocardial infarction, was 12 months. 201Tl SPECT study was positive for myocardial viability in 36 patients (65%) and negative in 19 patients (35%). Sensitivity, specificity, positive and negative predictive values for functional improvement in the follow-up period were 85%, 75%, 92% and 60%. Out of seven (13%) cardiac events in the follow-up period (four cardiac deaths and three reinfarctions), five occurred in 20 medically treated patients and two in 35 revascularized patients (25% vs 6%, P <0.05). Absence of myocardial viability was the only variable associated with adverse cardiac events (P =0.02). Survival at 12 months, as determined by using Kaplan-Meier analysis, was 56% for medically treated and non-viable patients, 80% for revascularized and non-viable patients, 91% for medically treated and viable patients, and 100% for revascularized and viable patients (P =0.0034). These findings suggest that in patients with previous myocardial infarction and mild-to-moderate myocardial dysfunction, the absence of myocardial viability as determined by the 201Tl SPECT study was the only variable associated with adverse cardiac events. The best 12 month survival was observed in revascularized viable patients, whereas the worse prognosis was found in non-viable, medically treated patients.

Dipyridamole-atropine-induced myocardial infarction in a patient with patent epicardial coronary arteries.

BACKGROUND: The diagnostic accuracy of the physical and pharmacological stress echocardiography tests is higher than routine exercise electrocardiography. They have an acceptable safety profile and have been rarely associated with severe adverse effects. CASE REPORT: We present a case of acute anterior myocardial reinfarction immediately after exercise and pharmacological (dipyridamole-atropine) stress echocardiography testing 1 month after successful stent implantation in LAD. Our patient was a 43-year-old man with a history of heavy smoking and hypertension. Remarkably, the stress echocardiogram was non-diagnostic few hours before the infarction occurred. Angiography performed 4 months after the reinfarction revealed neither a culprit lesion nor stent thrombosis. CONCLUSION: Aggressive "last generation" pharmacological stress testing may provide optimal diagnostic accuracy, but as in our case, complications may occur, even after negative stress testing. To our knowledge, this is the first reported case of an acute myocardial infarction as a severe complication of stress testing, which developed in a patient after stent implantation.

Pharmacological radionuclide ventriculography for detection of myocardial contractile reserve in patients after myocardial infarction: head-to-head comparison of low dose dobutamine and low dose dipyridamole.

BACKGROUND: Low dose pharmacological stress echocardiography with either dobutamine or dipyridamole infusion has been proposed for recognition of myocardial viability. However, dependence on adequate acoustic window, observer experience, and the mild degree of wall motion changes make the viability assessment by stress echocardiography especially bothersome. The objective of the study was to evaluate the ability of low dose dobutamine and low dose dipyridamole radionuclide ventriculography to detect contractile reserve in patients after myocardial infarction and functional recovery after coronary angioplasty. METHODS: The study group consisted of 20 consecutive patients (52 +/- 10 years, 17 male, 3 female) with previous myocardial infarction and resting regional dyssynergy, in whom diagnostic cardiac catheterization revealed significant one-vessel coronary artery stenosis suitable for angioplasty. Each patient underwent equilibrium 99m-Tc radionuclide ventriculography which was performed at rest and during low dose dipyridamole (0.28 mg/kg over 2 minutes) and low dose dobutamine infusion (up to 10 mcg/kg/min). Left ventricular global and regional ejection fractions were determined. Increase of regional ejection fraction for > 5% (inferoapical and posterolateral regions) or > 10% (anteroseptal regions) during low dose dobutamine and dipyridamole in infarcted regions, as well as in the followup period, was considered as index of contractile reserve. After 8 weeks of successful angioplasty, resting radionuclide ventriculography was repeated in all patients in order to identify functional recovery of the infarct zone. RESULTS: Out of the 180 analyzed segments (20 x 9), 90 regional ejection fractions have shown depressed contractility. The mean of the regional ejection fractions showing depressed contractility increased from the resting value of 34 +/- 12% to 42 +/- 14% in the follow-up period (p = 0.06). Of the 90 with baseline dyssynergy, 46 were responders during low-dose dobutamine (51%), whereas 32 segments were responders (36%, p = 0.05 vs. dobutamine) during low dose dipyridamole. Positive predictive value of dobutamine and dipyridamole for predicting functional recovery was 72% and 75% (p = ns), respectively. Negative predictive value of dobutamine and dipyridamole was 48% and 69% (p = 0.05), respectively. In the group of patients with most severe dyskinesia (regional ejection fraction < 35%, 42 segments) positive predictive value was 73% and 82%, while negative predictive value was 42% and 64% for low dose dobutamine and low dose dipyridamole respectively (p = ns). CONCLUSION: Although low dose dobutamine induced higher rate of positive responses during radionuclide ventriculography imaging, dipyridamole radionuclide ventriculography has shown superior, particularly negative, prognostic value for predicting functional recovery of infarcted regions.

Inter-observer variability in the reporting of dynamic evacuation proctography.

OBJECTIVE: To determine the degree of inter-observer variability between two reporters of dynamic evacuation proctography (DEP). PATIENTS AND METHODS: The videotapes of 136 patients who had undergone the investigation of DEP in a 1-year period were retrospectively and independently reported by two of the authors. The authors recorded the presence or absence of an anterior rectocoele (as well as size-small, medium or large), an intussusception, a rectal prolapse and any degree of non-relaxing puborectalis syndrome (NRPS). RESULTS: The results were analysed using the κ statistic. I.W.I. reported 18% of the proctograms as normal. S.G.S. reported 26% of the proctograms as normal. κ scores for agreement on the presence or absence of rectal prolapses, NRPS, intussusception and anterior rectocoeles between the two reporters were 0.79, 0.70, 0.54 and 0.82, respectively. CONCLUSION: Usefulness of an investigation is dependent upon its reproducibility and hence on the degree of inter-observer variability in its reporting. Our study shows that DEP is a useful investigation for delineating the mechanics of the pelvic floor and that consistency of reporting in our Department is good.

Integrated evaluation of relation between coronary lesion features and stress echocardiography results: the importance of coronary lesion morphology.

OBJECTIVES: The aim of this study was to analyze, in the same group of patients, the relationship between multiple variables of coronary lesion and results of exercise, dobutamine and dipyridamole stress echocardiography tests. BACKGROUND: Integrated evaluation of the relation between stress echocardiography results and angiographic variables should include not only the assessment of stenosis severity but also evaluation of other quantitative and qualitative features of coronary stenosis. METHODS: Study population consisted of 168 (138 male, 30 female, mean age 51+/-9 years) patients, on whom exercise (Bruce treadmill protocol), dobutamine (up to 40 mcg/kg/min) and dipyridamole (0.84 mg/kg over 10 min) stress echocardiography tests were performed. Stress echocardiography test was considered positive for myocardial ischemia when a new wall motion abnormality was observed. One-vessel coronary stenosis ranging from mild stenosis to complete obstruction of the vessel was present in 153 patients, and 15 patients had normal coronary arteries. The observed angiographic variables included particular coronary vessel, stenosis location, the presence of collaterals, plaque morphology according to Ambrose classification, percent diameter stenosis and obstruction diameter as assessed by quantitative coronary arteriography. RESULTS: Covariates significantly associated with the results of physical and pharmacological stress tests included for all three stress modalities presence of collateral circulation, percent diameter stenosis and obstruction diameter, as well as lesion morphology (p < 0.05 for all, except collaterals for dobutamine stress test, p = 0.06). By stepwise multiple logistic regression analysis, the strongest predictor of the outcome of exercise echocardiography test was only percent diameter stenosis (p = 0.0002). However, both dobutamine and particularly dipyridamole stress echocardiography results were associated not only with stenosis severity - percent diameter stenosis (dobutamine, p = 0.04; dipyridamole, p = 0.003) - but also, and even more strongly, with lesion morphology (dobutamine, p = 0.006; dipyridamole, p = 0.0009). As all of stress echocardiography results were significantly associated with percent diameter stenosis, the best angiographic cutoff in relation to the results of stress echocardiography test was: exercise, 54%; dobutamine, 58% and dipyridamole, 60% (p < 0.05 vs. exercise). CONCLUSIONS: Integrated evaluation of angiographic variables have shown that the results of dobutamine and dipyridamole stress echocardiography are not only influenced by stenosis severity but also, and even more importantly, by plaque morphology. The results of exercise stress echocardiography, although separately influenced by plaque morphology, are predominantly influenced by stenosis severity, due to a stronger exercise capacity in provoking myocardial ischemia in milder forms of coronary stenosis.

Coronary vasodilation without myocardial erection. Simultaneous haemodynamic, echocardiographic and arteriographic findings during adenosine and dipyridamole infusion.

AIM: The aim of this study was to evaluate simultaneously echocardiographic, haemodynamic and angiographic changes that occur during adenosine and dipyridamole infusion, in patients with one-vessel coronary artery stenosis. This would assess whether deterioration in left ventricular haemodynamics during vasodilator agent infusion is influenced by vasodilation per se, or the development of myocardial ischaemia. METHODS AND RESULTS: We performed adenosine (140 micrograms.kg-1.min-1 over 4 min) and dipyridamole (up to 0.84 mg.kg-1 over 10 min) stress echocardiography tests, together with angiographic and haemodynamic assessment, in 26 patients undergoing elective coronary angioplasty. In 12 of 26 patients, adenosine and dipyridamole tests were repeated 24 h after angioplasty. The criterion for echocardiography test positivity was the appearance of a new transient regional wall motion abnormality. Coronary angiograms were analysed with quantitative coronary arteriography. Adenosine and dipyridamole induced regional dysfunction in 18/26 (69%) and 14/26 (54%) patients before angioplasty, respectively (P = ns). In the echocardiography-positive patients, the percent diameter stenosis was significantly (P < 0.05) tighter stenosis than in the echocardiography-negative patients (adenosine, 66.6 +/- 8.3% vs 58.0 +/- 8.9%; dipyridamole, 69.2 +/- 7.1% vs 57.7 +/- 7.6%). During both tests, left ventricular end-diastolic pressure significantly increased (P < 0.05) in echocardiography-positive patients (adenosine, 9.8 +/- 2.7 mmHg to 13.5 +/- 4.1 mmHg; dipyridamole, 10.1 +/- 2.8 mmHg to 14.1 +/- 4.3 mmHg), but not in echocardiography-negative patients. In the patients who had undergone successful angioplasty (reduction to < 50% diameter stenosis), both adenosine and dipyridamole confirmed the arteriographic success of the procedure (echocardiography negative in all patients). In this group of patients, no significant change was observed in left ventricular end-diastolic pressure during adenosine or dipyridamole infusion. CONCLUSIONS: Intravenous infusion of either adenosine or dipyridamole was accompanied by an obvious increase in left ventricular end-diastolic pressure only in patients with induced wall motion abnormalities. Coronary vasodilation per se has no significant effect on left ventricular end-diastolic pressure when no ischaemia is induced, disproving any clinically significant 'erectile' and adverse effects of coronary vasodilation per se.

High dose adenosine stress echocardiography for noninvasive detection of coronary artery disease.

OBJECTIVES: The aim of this study was to assess the tolerability and incremental diagnostic value of high adenosine doses in stress echocardiography testing in patients with coronary artery disease (CAD). BACKGROUND: In comparison with other pharmacologic stress echocardiography tests, standard dose adenosine stress has sub-optimal sensitivity for detecting milder forms of CAD. METHODS: Adenosine stress echocardiography was performed in 58 patients using a starting dose of 100 micrograms/kg body weight per min over 3 min followed by 140 micrograms/kg per min over 4 min (standard dose). If no new wall motion abnormality appeared, the dose was increased to 200 micrograms/kg per min over 4 min (high dose). All patients underwent coronary angiography. Significant CAD was defined as > or = 50% diameter stenosis in at least one major coronary artery. Thirty-three patients had one-vessel and seven had multivessel CAD. Coronary angiographic findings were normal in 18 patients. RESULTS: The high adenosine dose caused a slight but significant increase over baseline values in rate-pressure product. Limiting side effects occurred in two patients during the standard dose protocol and in one patient receiving the high dose regimen. The test was stopped in 30 patients after the standard adenosine dose regimen because of a provoked new wall motion abnormality. The sensitivity of adenosine echocardiography with the standard dose was 75% (95% confidence interval [CI] 63% to 87%). After completion of the standard dose protocol, 28 patients continued testing with the high dose adenosine protocol. The overall sensitivity of adenosine echocardiography, calculated as cumulative, increased to 92% (95% CI 84% to 100%) with the high dose (p < 0.05). The specificity of adenosine testing was 100% and 88%, respectively, with the standard and high dose regimen (p = 0.617). CONCLUSIONS: We believe that use of a higher than usual adenosine dose protocol for stress testing may improve the diagnostic value of adenosine echocardiography, mainly by increasing sensitivity in patients with single-vessel disease without deterioration of the safety profile and with only a mild reduction in specificity.

Dipyridamole and dobutamine: competitors or allies in pharmacological stress echocardiography?

Stress echocardiography has become an accepted and cost-effective method for diagnosing coronary artery disease. However, as exercise stress echocardiography is a demanding technique, difficult to reproduce, pharmacological stress echocardiography has become very popular in recent years. The two most popular tests from the pharmacological stress echocardiography arena are dipyridamole and dobutamine. They have enabled the technical limitations inherent in exercise echocardiography to be overcome, and have provided the opportunity to obtain, during stress, images of unchanged quality in comparison to baseline. However, the sensitivity of both pharmacological stresses applied separately is less than ideal in patients with milder forms of coronary artery disease and in patients under therapy. To overcome this, a new generation of pharmacological stress tests, the combined dipyridamole-dobutamine tests were introduced. A combined dipyridamole-dobutamine echocardiography stress test should suggest that the agents are natural allies rather than competitors but in some instances they are applicable only in selected patients, and each pharmacological agent may be clinically contraindicated for administration. This is the message from a large scale study of recent years.