Safety, efficacy, and indications of beta-adrenergic receptor blockade to reduce heart rate prior to coronary CT angiography.

For selected indications, coronary computed tomographic (CT) angiography is an established clinical technology for evaluation in patients suspected of having or known to have coronary artery disease. In coronary CT angiography, image quality is highly dependent on heart rate, with heart rate reduction to less than 60 beats per minute being important for both image quality and radiation dose reduction, especially when single-source CT scanners are used. ß-Blockers are the first-line option for short-term reduction of heart rate prior to coronary CT angiography. In recent years, multiple ß-blocker administration protocols with oral and/or intravenous application have been proposed. This review article provides an overview of the indications, efficacy, and safety of ß-blockade protocols prior to coronary CT angiography with respect to different scanner techniques. Moreover, implications for radiation exposure and left ventricular function analysis are discussed.

Effectiveness of A Four-Week Diet Regimen, Exercise and Psychological Intervention for Weight Loss.

INTRODUCTION: Obesity is accompanied by restriction in the quality of life and an increased risk of morbidity and mortality. Cardiovascular, orthopedic, and metabolic disorders are among the possible consequences. In the management of obesity, a combination therapy that includes dietary, exercise, and behaviour modules has proven its worth. AIM: To evaluate the effect of weight-associated parameters, circulation associated parameters, glucose metabolism, body composition and life quality changes within a four-week inpatient rehabilitation program. MATERIALS AND METHODS: Fifty-two patients underwent a 4-week inpatient rehabilitation program consisting of nutrition therapy, behavioural therapy and exercise therapy modules at the Eleonoren Clinic of Winterkasten, Germany. RESULTS: The mean weight reduction of 52 obese patients 40 (76.9%) males, 12 (23.1%) females; mean age 46 years; mean Body Mass Index (BMI) 43,79 kg/m2) achieved was 7.1 kg (from 1.20 kg to 17.50 kg), and the BMI reduction was 2.3 kg/m2 (from 0.40 kg/m2 to 5.40 kg/m2). The excessive weight loss was highly significant (p<0.001). Weight reduction was accompanied by an improvement in the diabetic metabolic state (lowering of fasting blood-glucose 20 mg/dl, postprandial blood glucose 26 mg/dl, HbA1c 0.27%). In all 73% of the patients suffered from arterial hypertonia. The significant mean decline of systolic and diastolic blood pressure was 12.8 mmHg and 6.8 mmHg, respectively. The resting pulse was reduced by an average of 11 beats per minute. The Bioelectric Impedance Analysis (BIA) revealed a significant reduction of body fat content (p<0.001). The subjective impression of impaired life quality (SF-36 questionnaire) improved significantly. CONCLUSION: The study clearly shows that the inpatient rehabilitation program at the Eleonoren Clinic was suitable to enhance the physical and mental state of people with obesity. In a two-year follow-up program the patients should take care of a permanent lifestyle change toward an improved dietary, movement and health behaviour.

Turbulent flow as a cause for underestimating coronary flow reserve measured by Doppler guide wire.

BACKGROUND: Doppler-tipped coronary guide-wires (FW) are well-established tools in interventional cardiology to quantitatively analyze coronary blood flow. Doppler wires are used to measure the coronary flow velocity reserve (CFVR). The CFVR remains reduced in some patients despite anatomically successful coronary angioplasty. It was the aim of our study to test the influence of changes in flow profile on the validity of intra-coronary Doppler flow velocity measurements in vitro. It is still unclear whether turbulent flow in coronary arteries is of importance for physiologic studies in vivo. METHODS: We perfused glass pipes of defined inner diameters (1.5-5.5 mm) with heparinized blood in a pulsatile flow model. Laminar and turbulent flow profiles were achieved by varying the flow velocity. The average peak velocity (APV) was recorded using 0.014 inch FW. Flow velocity measurements were also performed in 75 patients during coronary angiography. Coronary hyperemia was induced by intra-coronary injection of adenosine. The APV maximum was taken for further analysis. The mean luminal diameter of the coronary artery at the region of flow velocity measurement was calculated by quantitative angiography in two orthogonal planes. RESULTS: In vitro, the measured APV multiplied with the luminal area revealed a significant correlation to the given perfusion volumes in all diameters under laminar flow conditions (r2 > 0.85). Above a critical Reynolds number of 500--indicating turbulent flow--the volume calculation derived by FW velocity measurement underestimated the actual rate of perfusion by up to 22.5 % (13 +/- 4.6 %). In vivo, the hyperemic APV was measured irrespectively of the inherent deviation towards lower velocities. In 15 of 75 patients (20%) the maximum APV exceeded the velocity of the critical Reynolds number determined by the in vitro experiments. CONCLUSION: Doppler guide wires are a valid tool for exact measurement of coronary flow velocity below a critical Reynolds number of 500. Reaching a coronary flow velocity above the velocity of the critical Reynolds number may result in an underestimation of the CFVR caused by turbulent flow. This underestimation of the flow velocity may reach up to 22.5 % compared to the actual volumetric flow. Cardiologists should consider this phenomena in at least 20 % of patients when measuring CFVR for clinical decision making.

The Effects of Nutritional Juice Supplementation on the Extent of Climacteric Symptoms: An Observational Study.

Objective. This study aims to evaluate the effect of daily dietary nutritional supplement on somatic, psychological, and urogenital symptoms in postmenopausal women. Material and Methods. In this study 28 healthy, symptomatic, peri- and postmenopausal women of 47-67 years of age were allocated to use the nutritional supplement JuicePLUS+®. Primary research parameters: Menopause Rating Scale (MRS) was used to assess menopausal symptoms at baseline and after 8 and 16 weeks of treatment. Secondary parameters: proliferation behaviour of vaginal smear was scored at baseline and after treatment. Results. Treatment with the supplement resulted in a reduction of somatic, psychological, and urogenital symptoms. The overall MRS score showed an average improvement of 44.01%. Most benefits were observed for the psychological symptoms irritability (60.55%) and physical and mental exhaustion (49.08%); modest effects were observed for hot flashes (44.86%) and sleeping problems (35.56%). There was a minor improvement in sexual problems; 6 women reported an increased libido. No statistically significant effect was found in vaginal dryness and proliferation behaviour of vaginal mucosa. No adverse effects were observed. Conclusion. Dietary nutritional supplement may constitute an effective alternative therapy to conventional alternative medicine for somatic, psychological, and sexual symptoms.

Angiographic assessment of collateral connections in comparison with invasively determined collateral function in chronic coronary occlusions.

BACKGROUND: The evaluation of new therapeutic modalities to induce collateral growth in coronary artery disease require improved methods of angiographic characterization of collaterals, which should be validated by quantitative assessment of collateral function. METHODS AND RESULTS: In 100 patients with total chronic occlusion of a major coronary artery (duration >2 weeks) collaterals were assessed angiographically by the Rentrop grading, by their anatomic location, and by a new grading of collateral connections (CC grade 0: no continuous connection, CC1: threadlike continuous connection, CC2: side branch-like connection). The interobserver variability was 10%. Collateral function was assessed by Doppler flow (average peak velocity) and pressure recordings distal to the occlusion before recanalization. A collateral resistance index (RColl) was calculated. Recruitable collateral flow was measured during a final balloon inflation >30 minutes after the baseline measurement. The comparison of the anatomic location, the Rentrop, and the collateral connection grade showed only for the latter an independent and significant relation with RColl. CC2 collaterals preserved regional left ventricular function better than did CC1 collaterals and provided a higher collateral flow reserve during adenosine infusion. CC0 collaterals were predominantly observed in recent occlusions of 2 to 4 weeks' duration, with the highest RColl. During balloon reocclusion, recruitable collateral function was best preserved with CC2 and least with CC0. CONCLUSIONS: The angiographic grading of collateral connections in total chronic occlusions could differentiate collaterals according to their functional capacity to preserve regional left ventricular function and was closely associated with invasively determined parameters of collateral hemodynamics.

Prolonged QTc interval and high B-type natriuretic peptide levels together predict mortality in patients with advanced heart failure.

BACKGROUND: The role of QTc interval prolongation in heart failure remains poorly defined. To better understand it, we analyzed the QTc interval duration in patients with heart failure with high B-type natriuretic peptide (BNP) levels and analyzed the combined prognostic impact of prolonged QTc and elevated BNP. METHODS AND RESULTS: QTc intervals were measured in 241 patients with heart failure who had BNP levels >400 pg/mL. QT interval duration was determined by averaging 3 consecutive beats through leads II and V4 on a standard 12-lead ECG and corrected by using the Bazett formula. QTc intervals were prolonged (>440 ms) in 122 (51%) patients and normal in 119 (49%). The BNP levels in these 2 groups were not significantly different (786+/-321 pg/mL in the prolonged QTc group versus 733+/-274 pg/mL in the normal QTc group, P=0.13). During 6 months of follow-up, 46 patients died, 9 underwent transplantation, and 17 underwent left ventricular assist device implantation. The deaths were attributed to pump failure (n=24, 52%), sudden cardiac death (n=18, 39%), or noncardiac causes (n=4, 9%). Kaplan-Meier survival rates were 3 times higher in the normal QTc group than in the prolonged QTc group (P<0.0001). On multivariate analysis, prolonged QTc interval was an independent predictor of all-cause death (P=0.0001), cardiac death (P=0.0001), sudden cardiac death (P=0.004), and pump failure death (P=0.0006). CONCLUSIONS: Prolonged QTc interval is a strong, independent predictor of adverse outcome in patients with heart failure with BNP levels >400 pg/mL.

Gender-related differences in acute aortic dissection.

BACKGROUND: Few data exist on gender-related differences in clinical presentation, diagnostic findings, management, and outcomes in acute aortic dissection (AAD). METHODS AND RESULTS: Accordingly, we evaluated 1078 patients enrolled in the International Registry of Acute Aortic Dissection (IRAD) to assess differences in clinical features, management, and in-hospital outcomes between men and women. Of the patients enrolled in IRAD (32.1%) with AAD, 346 were women. Although less frequently affected by AAD (32.1% of AAD), women were significantly older and had more often presented later than men (P=0.008); symptoms of coma/altered mental status were more common, whereas pulse deficit was less common. Diagnostic imaging suggestive of rupture, ie, periaortic hematoma, and pleural or pericardial effusion were more commonly observed in women. In-hospital complications of hypotension and tamponade occurred with greater frequency in women, resulting in higher in-hospital mortality compared with men. After adjustment for age and hypertension, women with aortic dissection die more frequently than men (OR, 1.4, P=0.04), predominantly in the 66- to 75-year age group. Moreover, surgical outcome was worse in women than men (P=0.013); type A dissection in women was associated with a higher surgical mortality of 32% versus 22% in men despite similar delay, surgical technique, and hemodynamics. CONCLUSIONS: Our analysis provides insights into gender-related differences in AAD with regard to clinical characteristics, management, and outcomes; important diagnostic and therapeutic implications may help shed light on aortic dissection in women to improve their outcomes.

Autologous intracoronary mononuclear bone marrow cell transplantation in chronic ischemic cardiomyopathy in humans.

BACKGROUND: Recent data suggest that transplantation of autologous bone marrow cells (BMC) may contribute to myocardial repair after acute myocardial infarction. We hypothesized that patients with chronic ischemic cardiomyopathy could also benefit from autologous BMC transplantation in addition to established heart failure therapy. METHODS AND RESULTS: Five patients with chronic ischemic cardiomyopathy caused by anterior myocardial infarction, 1.3+/-0.5 years ago and open infarct artery, received autologous mononuclear BMC transplantation via balloon catheter in the target vessel at the site of previous occlusion. Patients were followed up at 3 months (left heart catheterisation, 2D-echocardiography, dobutamine stress echocardiography, cardiopulmonary exercise testing) and at 12 months (2D-echocardiography, cardiopulmonary exercise testing). Follow-up examination showed no significant improvement neither in global, regional, and microvascular function, nor in physical performance. CONCLUSIONS: In this pilot trial intracoronary transplantation of autologous, mononuclear BMC did not lead to any significant improvement in myocardial function and physical performance of patients with chronic ischemic heart disease.

Lack of association between Chlamydia Pneumoniae serology and endothelial dysfunction of coronary arteries.

BACKGROUND: Recent publications brought up the hypothesis that an infection with Chlamydia Pneumoniae (CP) might be a major cause of coronary artery disease (CAD). Therefore, we investigated whether endothelial dysfunction (ED) as a precursor of atherosclerosis might be detectable in patients with previous infection with CP but without angiographic evidence of CAD. METHODS: We included 16 patients (6 male / 10 female) of 52 consecutive patients with normal coronary angiography who had typical angina pectoris and pathologic findings in the stress test. Exclusion criteria were: active smoker, elevated cholesterol, hypertension, age > 65 years, diabetes mellitus, treatment with ACE-inhibitors, or known CAD. Blood sample analysis for serum titer against CP (aCP-IgG) was performed after coronary angiography. We looked for endothelial dysfunction analyzing the diameter of the left anterior descending coronary artery (LAD) before and after acetylcholine (ACh) i. c. Quantitative analysis of luminal diameter (LD) was performed in at least two planes during baseline conditions and after ACh for 2 minutes in dosages of 7.2 microg/min and 36 microg/min with an infusion speed of 2 ml/min. Using Doppler guide wire, the coronary flow velocity was measured continuously in the LAD. The coronary flow velocity reserve (CFVR) was measured after 20 microg adenosine i. c. RESULTS: 10 patients had an elevated aCP-IgG (> 1:8). 6 patients with negative titers (aCP-IgG

Comparison of left ventricular systolic and diastolic function in patients with idiopathic dilated cardiomyopathy and mild heart failure versus those with severe heart failure.

The pathogenesis of acute pulmonary edema in idiopathic dilated cardiomyopathy (IDC) is not completely understood. Because pulse-wave tissue Doppler imaging (TDI) allows a direct comparison between systolic as well as diastolic wall motion velocities, we tested the hypothesis that acute pulmonary edema is caused by both systolic and diastolic failure. We prospectively studied 65 patients. Forty patients had IDC (group 1), 15 of whom had recent-onset pulmonary congestion (group 1a, New York Heart Association [NYHA] functional classes III and IV) and 25 of whom were in clinically stable condition without signs of pulmonary congestion (group 1b, NYHA I and II). All of these patients were restudied after 3, 7, and 45 days. Groups 1a and 1b were compared with 25 subjects without evidence of heart disease (group 2). Peak systolic wall motion velocity (Vs), peak wall motion velocity of the early (Ve), and late (Va) filling waves were measured by TDI; mitral inflow pattern was determined by pulse-wave Doppler and left ventricular (LV) ejection fraction (EF) by 2-dimensional echocardiography. In those patients without pulmonary edema (controls and group 1b, n = 50), we found a positive correlation between LVEF and Vs (r = 0.72, p <0.001) and between LVEF and Ve (r = 0.79, p <0.001). Early diastolic wall motion velocity always exceeded peak systolic wall motion velocity (Ve/Vs ratio >1). In patients with IDC with recent-onset pulmonary congestion (group 1a), Ve was significantly lower compared with group 1b (3.5 +/- 0.2 vs 4.9 +/- 0.4 cm/s, p <0.01, Ve/Vs ratio <1). Clinical improvement was paralled by a gradual increase in Ve (3.5 +/- 0.2 to 6.8 +/- 0.3 cm/s, p <0.01) but not in Vs or LVEF. Thus, in patients with IDC acute pulmonary edema is exclusively caused by diastolic rather than systolic failure.

Studies on intragastric PCO2 at rest and during exercise as a marker of intestinal perfusion in patients with chronic heart failure.

AIMS: The aim of this study was to investigate mesenteric ischaemia by determining intragastric PCO(2) (iPCO(2)) with gastric tonometry during rest and exercise stress testing in patients with chronic heart failure (CHF). In CHF inflammatory immune activation is hypothesized to result from a chronic endotoxin challenge due to bacterial translocation of hypoperfused intestinal mucosa. METHODS AND RESULTS: In 10 patients with CHF and ten healthy controls a tonometry catheter was inserted into the stomach. IPCO(2) was measured at rest and during bicycle exercise every 5 min. At rest arterial pCO(2) (aPCO(2)), intragastric pCO(2) (iPCO(2)) and the intragastric/arterial gap did not differ between patients and controls. During low level exercise (25 W), patients showed an increase in iPCO(2) compared to resting iPCO(2), whereas controls did not show an increase in iPCO(2) (change in iPCO(2): 12+/-2% vs. 1+/-0.4%, P<0.001). In CHF, iPCO(2) during peak exercise was 25+/-3% higher than at rest, compared to controls (increase 2+/-1, P<0.0001). CONCLUSIONS: Patients with CHF already at low level exercise develop an increase in iPCO(2). This is likely to reflect hypoperfusion of the intestinal mucosa, which may contribute to the development of bacterial translocation.

Lack of regeneration of myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans with large anterior myocardial infarctions.

BACKGROUND: Experimental and preliminary clinical data suggest that transplantation of autologous bone marrow cells (BMC) may contribute to regeneration of the myocardium after acute myocardial infarction. This approach should be tested in patients with large infarctions in whom a positive effect would be most beneficial. METHODS AND RESULTS: After successful recanalization within 5.9 +/- 2.5 h and stent implantation in five patients with a large acute anterior myocardial infarction (AMI), the patients received autologous mononuclear BMCs via a balloon catheter placed into the left anterior descending artery 6.3 +/- 0.4 days after revascularization. At 3-month follow-up, no improvement was observed for left ventricular ejection fraction, regional wall motion in the infarcted zone, contractility index measured via dobutamine stress echocardiography, coronary blood flow reserve and maximal oxygen uptake, respectively. After further follow-up of 12 months, again no change of the left ventricular ejection fraction could be detected. CONCLUSIONS: Intracoronary transplantation of autologous mononuclear BMCs did not improve cardiac function in our patients with large anterior myocardial infarctions after 3 and 12 months.

[Evidence-based application of cardiac magnetic resonance and cardiac computed tomography for primary diagnosis of stable coronary artery disease with special attention to disease management programs and the German National Medical Care Guidelines]. / Evidenzbasierter Einsatz von Kardio-MR und Kardio-CT in der Primärdiagnostik der stabilen koronaren Herzkrankheit unter besonderer Berücksichtigung des Disease-Management-Programms (DMP) KHK und der Nationalen Versorgungsleitlinie.

BACKGROUND AND PURPOSE: Despite all the progress made in diagnosis and treatment, cardiovascular diseases remain the no. 1 cause of death worldwide. In 2005, 27.9% of males and 24.1% of females (eight times more than for mammary carcinoma) in Germany died of coronary artery disease (CAD). Although mortality rates following acute myocardial infarction have considerably dropped, morbidity has increased--people are getting older, but they are getting older sick. The resulting need for reduction of CAD morbidity can only be achieved by truly early detection of patients at high coronary risk before occurrence of a coronary event. Modern imaging techniques like cardiac magnetic resonance (MR) and cardiac computed tomography (CT) are being increasingly utilized. The goal of this review is the practical application of evidence-based recommendations by relevantly and cost-effectively implementing cardiac MR and cardiac CT with special attention to current national and international guidelines and recommendations. THE PATIENT WITH STABLE CHEST PAIN: The primary objective here is to ascertain if the described symptoms can be attributed to a stenosing CAD with inducible myocardial ischemia or if they are effected by extracardial sources. As always, patients' history, examination findings and the stress ECG play the major roles. The conventional approach prescribes that an abnormal resting ECG compromising the interpretation of a stress ECG, should immediately be followed by an imaging ischemia diagnosis technique, like stress echocardiography, myocardial scintigraphy or cardiac MR (recommendation I B). This also holds true when a stress ECG is assessable and the probability of a stenosing CAD is between 10% and 90% (recommendation I B or "appropriate"). Alternatively, "modern" procedures allow imaging ischemia diagnosis to be replaced by noninvasive coronary angiography using a CTA (recommendation IIa B). If the image quality by CTA is assessable (free of artifacts and no disruptive calcified plaques) and no coronary stenosis can be found, the coronary diagnosis process may at this point be terminated, avoiding superfluous cardiac catheterizations. If the CTA shows the possibility of a higher-grade coronary stenosis, a cardiac catheterization examination with stand-by PCI (percutaneous coronary intervention) can be performed. THE ASYMPTOMATIC PREVENTION PATIENT: The prim ary objective in cardiovascular primary prevention is the avoidance of a first myocardial infarction and/or a first stroke. Current guidelines for prevention of cardiovascular diseases recommend administration of acetylsalicylic acid (ASA) and a statin when risk>20%/10 years (recommendation I A). The coronary calcium score has a strong predictive power which is independent of conventional risk factors and thus offers the most relevant information in addition to Framingham, PROCAM or ESC scores regarding coronary risk. For patients initially showing "intermediate" coronary risk (10-20%), guidelines suggest the determination of the coronary calcium score, which leads to better risk assessment and to identification of patients needing more aggressive lipid lowering (recommendation IIb B). Thus, the cardiac CT, on the one hand, aims the intense risk reduction needed in primary prevention to the high-risk patients, on the other hand, it avoids "superfluous" cardiac catheterizations, unnecessary statin therapies and potentially harmful ASA administrations. However, the proof of coronary calcium must not be confused with the presence of coronary artery stenoses: a positive calcium score in an asymptomatic person does not by itself indicate the need for a cardiac catheterization.

[The European Society of Cardiology (ESC) guidelines for percutaneous coronary interventions (PCI). Three case reports]. / Die ESC-Leitlinien zur perkutanen Koronarintervention (PCI) : Drei Fallbeispiele.

The European Society of Cardiology (ESC) for the first time issued guidelines for percutaneous coronary interventions (PCI) in spring 2005. The strengths of recommendations stated in the ESC guidelines (as in those of the AHA/ACC [American Heart Association/American College of Cardiology]) are traditionally a combination of recommendation classes (I, IIa, and IIb) and a level of evidence (A, B, or C). This paper explains and discusses selected focal points of the ESC PCI guidelines based on three representative cases from daily practice. 1. Stable coronary artery disease (CAD): PCI in a 53-year-old patient without angina pectoris and proof of myocardial ischemia. With a clear indication of ischemia in the anterior myocardial wall, the ESC PCI guidelines indicated coronary angiography with possible PCI, even without angina pectoris symptoms. Cardiac catheterization showed a 99% proximal LAD stenosis, which was immediately dilated and stented based on the indicated ischemia. According to the ESC PCI guidelines, an intervention is indicated for CAD when a larger ischemic area is clearly evident even in the absence of typical angina (recommendation class I A). 2. ST segment elevation myocardial infarction (STEMI): PCI even after successful thrombolysis. A 70-year-old patient experienced acute substernal pain and immediately went to his nearby hospital. The ECG clearly showed anterior myocardial wall STEMI, which in this hospital without a cardiac cath lab indicated thrombolysis, since it could be initiated within 3 h after the onset of chest pain. Pain relief was evident soon after thrombolysis, combined with a resolution of the ST segment elevations. As suggested by the ESC PCI guidelines, a transfer to a cardiac cath lab took place the next day, where the 50% residual stenosis of the LAD was stented. The ESC PCI guidelines suggest coronary angiography with possible PCI within 1-2 days following successful thrombolysis (recommendation class I A). Thus, even "successful" thrombolysis is not regarded as the final treatment for STEMI. 3. Premature termination of clopidogrel after stent implantation: stent thrombosis with acute myocardial infarction. A 46-year-old patient visited the practice due to increasing dyspnea. 4 months earlier, a Taxus stent had been implanted at a heart center into the second RPLS of the RCX; 3 days later, a Cypher stent was implanted in the LAD. Upon being discharged on a Friday at noon, the patient was advised to see his general practitioner soon to attain a prescription for clopidogrel. The patient was given an appointment at his general practitioner for the following Wednesday afternoon. But on that Wednesday morning the patient went into cardiogenic shock. Although the occluded LAD (stent thrombosis) could be quickly reopened, left ventricular myocardium became severely damaged. Until a cardiac transplantation will be performed, a defibrillator was implanted. This "organizational" gap in clopidogrel administration did not conform to the ESC PCI guidelines: after implantation of any coronary stent, dual antiplatelet treatment (acetylsalicylic acid and clopidogrel) must be consistently administered for at least 4 weeks. After implantation of drug-eluting stents (DES), the ESC PCI guidelines call for clopidogrel administration for at least 6 months; when small vessels, long lesions or a complex anatomy (e. g., bifurcation stenting) are involved, a duration of 1 year or even longer is recommended. The optimal duration of platelet aggregation inhibition following PCI with DES of unprotected left main stem stenoses is unknown at this time. The traditional levels of evidence according to ESC, AHA and ACC criteria (levels A, B, or C) do no longer meet the actual requirements to assess the scientific evidence of randomized PCI trials and registry studies. For example, only two small randomized studies with few patients and insufficient statistical power utilizing a clinically insignificant surrogate endpoint would be enough to attain level of evidence A. Consequently, a new scoring system will be proposed, which considers criteria such as the importance of a primary clinical endpoint, the statistical power achieved, and the presence of an independent external data review and safety monitoring board.

Impaired acute collateral recruitment as a possible mechanism for increased cardiac adverse events in patients with diabetes mellitus.

BACKGROUND: The mortality of coronary artery disease is increased in diabetic patients. An impaired collateral function is considered a possible explanation. This study should assess the influence of diabetes on collaterals by direct invasive assessment of collateral function. METHODS: In 90 consecutive patients with a chronic coronary occlusion (TCO) of >2 weeks duration a recanalization was done. Thirty patients with diabetes (33%) were compared with 60 (67%) without diabetes. Blood flow velocity and pressure were measured distal to the occlusion by intracoronary Doppler and pressure wires before PTCA, and again after PTCA during a final balloon reocclusion to assess acute recruitment of collaterals. Resistance indexes for collaterals (R(Coll)) and peripheral microcirculation (R(P)) were calculated. RESULTS: The R(Coll)(diabetics: 8.1+/-6.8 vs nondiabetics: 8.7+/-6.7 mmHg cm(-1)s(-1); p=0.68) and R(P)(5.6+/-4.2 vs 6.6+/-3.8 mmHg cm(-1)s(-1); p=0.30) were similar in diabetic and nondiabetic patients before recanalization. During balloon reocclusion both R(Coll)and R(P)increased. This increase was significantly more pronounced in diabetic than in nondiabetic patients in TCOs <3 months duration. In TCOs of longer duration (> or =3 months) these differences were no longer detectable between both patient groups. CONCLUSIONS: Diabetic patients with TCOs have similarly developed collaterals as nondiabetic patients. However, in TCOs <3 months duration the acute recruitment of collaterals in case of reocclusion is impaired. This could explain some of the higher complication rate and mortality after coronary interventions in diabetic patients.

No influence of hemochromatosis-related gene mutations on restenosis rate in a retrospective study of 137 patients after coronary stent implantation.

BACKGROUND: Recent publications have shown an increased risk of coronary artery disease and myocardial infarction in patients with alteration of the hemochromatosis-related gene (HFE gene). The HFE gene mutation is associated with elevated iron uptake and serum iron overloading. Iron plays an important role in promoting the oxidation of LDL cholesterol. The iron deposition in the endothelium and in the media is closely associated with the progression of atherosclerosis. However, it is unclear whether the mutation of the HFE gene also influences the rate of restenosis after coronary stent implantation. METHODS: In a retrospective analysis, 137 patients (pts.) who underwent elective coronary stent implantation were angiographically reevaluated after six months. All patients were part of the OPTICUS-study population which investigated optimized stent implantation guided by intravascular ultrasound. Computerized quantitative analysis was performed in all procedures in a double-blinded fashion. At six-month follow-up, DNA fragments containing the substitution of tyrosine for cytosine at codon 282 were amplified by PCR. The results were analyzed by polyacrylamide gel electrophoresis. Statistical analysis was performed by multivariate linear regression. RESULTS: According to the HFE gene polymorphism we formed two subgroups: 129 pts. (94%) did not show changes in HFE gene (NH), 8 pts. (6%) were heterozygous for HFE Cys282Tyr (H). The groups did not differ in age, gender, extent of coronary artery disease, initial degree and length of stenosis and all patients underwent re-angiography. At six-month follow-up the average luminal narrowing in the stented vessel was 36.2 +/- 20.3% in the NH group compared with 27.8 +/- 20.0% in the H group which was statistically not significant (n. s.). The minimal luminal diameter was 1.9 +/- 0.71 mm in the NH group and 2.2 +/- 0.66 mm in the H group respectively (n. s.). 33 pts (26%) in the NH group versus 2 pts (25%) in the H group had >/= 50% diameter narrowing at follow-up (n. s.). The odds ratio of stent restenosis in H patients was 0.932. CONCLUSIONS: The authors did not find any association between restenosis rate and HFE gene alteration and therefore, we conclude that the polymorphism of the HFE gene is not a risk factor for restenosis after coronary stent implantation.