Improvement of electrical synchrony in cardiac resynchronization therapy using dynamic atrioventricular delay programming and multipoint pacing.

BACKGROUND: Optimization of cardiac resynchronization therapy (CRT) is often time-consuming and therefore underused in a clinical setting. Novel device-based algorithms aiming to simplify optimization include a dynamic atrioventricular delay (AVD) algorithm (SyncAV, Abbott) and multipoint pacing (MPP, Abbott). This study examines the acute effect of SyncAV and MPP on electrical synchrony in patients with newly and chronically implanted CRT devices. METHODS: Patients with SyncAV and MPP enabled devices were prospectively enrolled during implant or scheduled follow-up. Blinded 12-lead electrocardiographic acute measurements of QRS duration (QRSd) were performed for intrinsic QRSd (Intrinsic), bi-ventricular pacing (BiV), MPP, BiV with SyncAV at default offset 50 ms (BiVSyncAVdef ), BiV with SyncAV at patient-specific optimised offset (BiVSyncAVopt ), MPP with SyncAV at default offset 50 ms (MPPSyncAVdef ), and MPP with SyncAV at patient-specific optimised offset (MPPSyncAVopt ). RESULTS: Thirty-three patients were enrolled. QRSd for Intrinsic, BiV, MPP, BiVSyncAVdef , BiVSyncAVopt , MPPSyncAVdef , MPPSyncAVopt were 160.4 ± 20.6 ms, 141.0 ± 20.5 ms, 130.2 ± 17.2 ms, 121.7 ± 20.9 ms, 117.0 ± 19.0 ms, 121.2 ± 17.1 ms, 108.7 ± 16.5 ms respectively. MPPSyncAVopt led to greatest reduction of QRSd relative to Intrinsic (-31.6 ± 11.1%; p < .001), showed significantly shorter QRSd compared to all other pacing configurations (p < .001) and shortest QRSd in every patient. Shortening of QRSd was not significantly different between newly and chronically implanted devices (-51.6 ± 14.7 ms vs. -52.7 ± 21.9 ms; p = .99). CONCLUSION: SyncAV and MPP improved acute electrical synchrony in CRT. Combining both technologies with patient-specific optimization resulted in greatest improvement, regardless of time since implantation. Whats new Novel device-based algorithms like a dynamic AVD algorithm (SyncAV, Abbott) and multipoint pacing (MPP, Abbott) aim to simplify CRT optimization. Our data show that a combination of patient tailored SyncAV optimization and MPP results in greatest improvement of electrical synchrony in CRT measured by QRS duration, regardless if programmed in newly or chronically implanted devices. This is the first study to our knowledge to examine a combination of these device-based algorithms. The results help understanding the ideal ventricular excitation in heart failure.

Feasibility of the Figure-of-8-Suture as Venous Closure in Interventional Electrophysiology: One Strategy for All?

Background: Venous vascular access with higher sheath size is common in interventional electrophysiology. In contrast to arterial vascular access, no dedicated closure devices exist for closure after venous access with higher sheath sizes. The Figure-of-8-Suture, an easy to apply suture, may be as a feasible approach for closure venous puncture. Our aim was to evaluate the feasibility of closure of femoral venous access. Methods: From November 2016 to February 2018, patients undergoing electrophysiological procedures, closure of left atrial appendage or patent foramen ovale were included. Until May 2017, manual compression was performed to achieve haemostasis at venous access site (control group). From May 2017, patients were treated with a Figure-of-8-Suture (treatment group, Figure 1). Turnaround time and incidence of vascular complications were compared between the two groups. Results: In total, 290 patients were included, 132 in the control group and 158 in the Figure-of-8-Suture group. Hemostasis after sheath removal was achieved in 100% of the cases in the control group by manual compression and in 98.7% of the cases with the Figure-of-8-Suture (p=0.2). Vascular complications were more common in the control group (6.8 vs. 1.3 %, p=0.01). Turnaround time was significantly lower in the Figure-of-8-Suture group (58.6 ± 14 vs. 77 ± 33.9 min, p=0.004). In a sub-analysis in obese patients with body mass index (BMI) ≥30 kg/m2 (Figure-of-8 n=45, controls n=35), vascular complications were significantly more common in the control group (9.4 vs 0%, p=0.045). Conclusion: The Figure-of-8-Suture is an easy-to-apply, effective approach for venous closure after electrophysiological procedures.

Subcutaneous cardioverter defibrillator implanted intermuscularly in patients with end-stage renal disease requiring hemodialysis: 5-year follow-up.

BACKGROUND: The aim of the present study was to evaluate the long-term safety and effectiveness of the subcutaneous implantable cardioverter defibrillator (S-ICD) when implanted intermuscularly in patients with end-stage renal disease and hemodialysis. METHODS: This study is a retrospective analysis of 21 consecutive patients implanted with S-ICDs at three experienced centers in Germany with comorbid renal insufficiency requiring hemodialysis, as well as being at risk of sudden cardiac death. The S-ICD was placed intermuscularly in all patients. Follow-ups (FUs) were performed every 6 months. RESULTS: The mean ± standard deviation FU duration was 60.0 ± 11.4 months, with a range of 39 to 78 months. There were no deaths due to arrhythmia, or device-associated infections and complications. Four patients (19.1%) died during FU due to respiratory insufficiency during dialysis, systolic heart failure, septic infection of the urogenital tract, and colorectal cancer, respectively. There were six non-device-related hospitalizations with a duration of 12.7 ± 5.1 days and a hospitalization rate of 4.1 per 100 patient years. CONCLUSIONS: In the long-term FU of this small population of seriously compromised hemodialysis patients at risk of sudden cardiac death, the intermuscularly implanted S-ICD system was safe and effective. No arrhythmic complications, device-associated infections, or complications compromised survival. These data are encouraging and support testing in a larger group of similarly compromised patients.

Subcutaneous versus Transvenous Implantable Cardioverter Defibrillator in Patients with End-Stage Renal Disease Requiring Dialysis: Extended Long-Term Retrospective Multicenter Follow-Up.

BACKGROUND: Implantable cardioverter defibrillators (ICD) prevent sudden cardiac death (SCD). Patients with end-stage renal disease (ESRD) requiring dialysis are at a very high risk of infection from cardiac implantable electronic device (CIED) implantation as well as mortality. In the present study, we compared the long-term complications and outcomes between subcutaneous ICD (S-ICD) and transvenous ICD (TV-ICD) recipients. METHODS: In this retrospective analysis, we analyzed a total of 43 patients with ESRD requiring dialysis who received either a prophylactic S-ICD (26 patients) or a single right ventricular lead TV-ICD (17 patients) at seven experienced centers in Germany. Follow-up was performed bi-annually, at the end of which the data concerning comorbidities and, if applicable, reason for death were checked and confirmed with patients' general practitioner, nephrologist and cardiologist. RESULTS: The median follow up duration was 95.6 months (range 42.8-126.3 months). Baseline characteristics were without noteworthy significant differences between groups. During follow-up (FU), there were significantly more device-associated infections (HR 8.72, 95% confidence interval (CI), 1.18 to 12.85, p < 0.05) and device-associated hospitalizations (HR 10.20, 95% CI 1.22 to 84.61, p < 0.001), as well as a higher cardiovascular mortality (HR 9.17, 95% CI 1.12 to 8.33, p < 0.05), in the TV-ICD group. The number of patients requiring hospitalization for any reason was significantly higher in the TV-ICD group (HR 2.59, 95% CI 1.12 to 6.41, p < 0.05). There was no significant difference in overall mortality (HR 1.92, 95% CI 0.96 to 6.15, p = 0.274). CONCLUSIONS: Our data suggest that, in this extended follow-up in seriously compromised renal patients on dialysis, the S-ICD patients have statistically fewer device infections and hospitalizations as well as lower cardiac mortality compared with the TV-ICD cohort.

Comparison of infection and complication rates associated with transvenous vs. subcutaneous defibrillators in patients with stage 4 chronic kidney disease: a multicenter long-term retrospective follow-up.

Background: Patients with progressive chronic kidney disease (CKD) are at higher risk of infections and complications from cardiac implantable electronic devices (CIED). In patients with a primary or secondary prophylactic indication, implantable cardiac defibrillators (ICD) can prevent sudden cardiac deaths (SCD). We retrospectively compared transvenous-ICD (TV-ICD) and intermuscularly implanted subcutaneous-ICD (S-ICD) associated infections and complication rates together with hospitalizations in recipients with stage 4 kidney disease. Methods: We retrospectively analyzed 70 patients from six German centers with stage 4 CKD who received either a prophylactic TV-ICD with a single right ventricular lead, 49 patients, or a S-ICD, 21 patients. Follow-Ups (FU) were performed bi-annually. Results: The TV-ICD patients were significantly older. This group had more patients with a history of atrial arrhythmias and more were prescribed anti-arrhythmic medication compared with the S-ICD group. There were no significant differences for other baseline characteristics. The median and interquartile range of FU durations were 55.2 (57.6-69.3) months. During FU, patients with a TV-ICD system experienced significantly more device associated infections (n = 8, 16.3% vs. n = 0; p < 0.05), device-associated complications (n = 13, 26.5% vs. n = 1, 4.8%; p < 0.05) and device associated hospitalizations (n = 10, 20.4% vs. n = 1, 4.8%; p < 0.05). Conclusion: In this long-term FU of patients with stage 4 CKD and an indication for a prophylactic ICD, the S-ICD was associated with significantly fewer device associated infections, complications and hospitalizations compared with TV-ICDs.

First responder for in-hospital resuscitation: 5-year experience with an automated external defibrillator-based program.

BACKGROUND: The survival of in-hospital cardiac arrest (8-25%) has not changed substantially in the past. Until now, most hospitals in Germany had no standardized protocols available for a course of action in case of emergency, and there are no continuous registry data for in-hospital cardiac arrest and survival. OBJECTIVE: Our aim was to improve survival and receive outcomes data, so we implemented a structured hospital-wide automated first-responder system in the hospital. Here our 5-year experience with 443 emergency calls is outlined. METHODS: Throughout the hospital, 15 automated external defibrillator (AED) "access spots," which can be easily reached within 30 s, were identified. AEDs were then installed at these locations (Lifepak 500 and Lifepak 1000, Medtronic equipped with a Biolog 3000i portable ECG monitor). At the same time, a training program was initiated in which the employees of the hospital participated once a year. Participants learned how to apply and activate an AED in case of cardiac arrest even before the designated Cardiac Arrest Team arrived at the scene. RESULTS: A witnessed cardiac arrest event was confirmed in 126 cases. In 56 of the 126 cases, the primary arrest rhythm was either ventricular tachycardia or ventricular fibrillation and the AED delivered a shock. In this group, spontaneous circulation was reached in 44 cases (79%) and 23 patients (41%) were discharged. In 44% (24 from 55 patients) of the cases, a shock was recommended by AED and delivered by the first responders before the rescue team arrived. CONCLUSIONS: The first-responder AED program successfully gave training lessons to the hospital staff. The training included how to initiate the cardiac arrest call, how to use the AED, and how to start immediate resuscitation. As a result, a higher survival rate after in-hospital cardiac arrest can be accomplished.

Stepwise Approach for Transvenous Lead Extraction in a Large Single Centre Cohort.

BACKGROUND: Infection, lead dysfunction and system upgrades are all reasons that transvenous lead extraction is being performed more frequently. Many centres focus on a single method for lead extraction, which can lead to either lower success rates or higher rates of major complications. We report our experience with a systematic approach from a less invasive to a more invasive strategy without the use of laser sheaths. METHODS: Consecutive extraction procedures performed over a period of seven years in our electrophysiology laboratory were included. We performed a stepwise approach with careful traction, lead locking stylets (LLD), mechanical non-powered dilator sheaths, mechanical powered sheaths and, if needed, femoral snares. RESULTS: In 463 patients (age 69.9 ± 12.3, 31.3% female) a total of 780 leads (244 ICD leads) with a mean lead dwelling time of 5.4 ± 4.9 years were identified for extraction. Success rates for simple traction, LLD, mechanical non-powered sheaths and mechanical powered sheaths were 31.5%, 42.7%, 84.1% and 92.6%, respectively. A snare was used for 40 cases (as the primary approach for 38 as the lead structure was not intact and stepwise approach was not feasible) and was successful for 36 leads (90.0% success rate). Total success rate was 93.1%, clinical success rate was 94.1%. Rate for procedural failure was 1.1%. Success for less invasive steps and overall success for extraction was associated with shorter lead dwelling time (p < 0.001). Major procedure associated complications occurred in two patients (0.4%), including one death (0.2%). A total of 36 minor procedure-associated complications occurred in 30 patients (6.5%). Pocket hematoma correlated significantly with uninterrupted dual antiplatelet therapy (p = 0.001). Pericardial effusion without need for intervention was associated with long lead dwelling time (p = 0.01) and uninterrupted acetylsalicylic acid (p < 0.05). CONCLUSION: A stepwise approach with a progressive invasive strategy is effective and safe for transvenous lead extraction.

Success and safety of deep sedation as a primary anaesthetic approach for transvenous lead extraction: a retrospective analysis.

There is a rising number in complications associated with more cardiac electrical devices implanted (CIED). Infection and lead dysfunction are reasons to perform transvenous lead extraction. An ideal anaesthetic approach has not been described yet. Most centres use general anaesthesia, but there is a lack in studies looking into deep sedation (DS) as an anaesthetic approach. We report our retrospective experience for a large number of procedures performed with deep sedation as a primary approach. Extraction procedures performed between 2011 and 2018 in our electrophysiology laboratory have been included retrospectively. We began by applying a bolus injection of piritramide followed by midazolam as primary medication and would add etomidate if necessary. For extraction of leads a stepwise approach with careful traction, locking stylets, dilator sheaths, mechanical rotating sheaths and if needed snares and baskets has been used. A total of 780 leads in 463 patients (age 69.9 ± 12.3, 31.3% female) were extracted. Deep sedation was successful in 97.8% of patients. Piritramide was used as the main analgesic medication (98.5%) and midazolam as the main sedative (94.2%). Additional etomidate was administered in 15.1% of cases. In 2.2% of patients a conversion to general anaesthesia was required as adequate level of DS was not achieved before starting the procedure. Sedation related complications occurred in 1.1% (n = 5) of patients without sequalae. Deep sedation with piritramide, midazolam and if needed additional etomidate is a safe and feasible strategy for transvenous lead extraction.

First-in-man experience with a new 7F vascular closure device (EXOSEAL™): the 7F ECLIPSE study.

OBJECTIVE: This feasibility study examined safety and effectiveness of the new EXOSEAL™ Vascular Closure Device (VCD) designed to promote hemostasis and early ambulation after percutaneous procedures. BACKGROUND: Most VCDs currently approved by the United States FDA have been associated with significantly shorter time-to-hemostasis (TTH) and time-to-ambulation (TTA) compared to standard manual or mechanical compression, but their ease of use, patient comfort during deployment, and safety profiles are variable. METHODS: Patients underwent diagnostic or interventional procedures using 7F introducer sheaths. Primary safety endpoint was the 30-day combined rate of access-related complications and primary effectiveness endpoints were TTH and TTA. RESULTS: Sixty patients were enrolled prospectively (mean age 63.3 ± 11.3 year, 17% diabetics). Device and procedural success was achieved in 92% and 93%, respectively. Mean TTH and TTA was 3.2 ± 3.0 minutes and 3.0 ± 6.2 hours, respectively. No deaths or serious access-related adverse events occurred. A ≥6 cm access-site hematoma was the only adverse event, observed in 3 patients. CONCLUSIONS: Use of the 7F EXOSEAL™ VCD was associated with short TTH and TTA, as well as low rates of procedural and 30-day access-related complications.

Long-Term Performance Comparison of Bipolar Active vs. Quadripolar Passive Fixation Leads in Cardiac Resynchronisation Therapy.

Background: Bipolar active fixation (BipolarAFL) and quadripolar passive fixation left-ventricular leads (QuadPFL) have been designed to reduce the risk of phrenic nerve stimulation (PNS), enable targeted left-ventricular pacing, and overcome problems of difficult coronary venous anatomy and lead dislodgment. This study sought to report the long-term safety and performance of a BipolarAFL, Medtronic Attain Stability 20066, compared to QuadPFL. Methods: We performed a single-operator retrospective analysis of 81 patients receiving cardiac resynchronization therapy (CRT) (36 BipolarAFL, 45 QuadPFL). Immediate implant data and electrical and clinical data during follow-up (FU) were analyzed. Results: BipolarAFL has been chosen in patients with significantly larger estimated vein diameter (at the lead tip: 7.2 ± 4.1 Fr vs. 4.1 ± 2.3 Fr, p < 0.001) without significant time difference until the final lead position was achieved (BipolarAFL: 20.9 ± 10.5 min, vs. QuadPFL: 18.9 ± 8.9 min, p = 0.35). At 12 month FU no difference in response rate to CRT was recorded between BipolarAFL and QuadPFL according to left ventricular end-systolic volume (61.1 vs. 60.0%, p = 0.82) and New York Heart Association (66.7 vs. 62.2%, p = 0.32). At median FU of 48 months (IQR: 44-54), no lead dislodgment occurred in both groups but a significantly higher proportion of PNS was recorded in QuadPFL (13 vs. 0%, p < 0.05). Electrical parameters were stable during FU in both groups without significant differences. Conclusion: BipolarAFL can be implanted with ease in challenging coronary venous anatomy, shows excellent electrical performance and no difference in clinical outcome compared to QuadPFL.

Circulating endothelial microparticles correlate inversely with endothelial function in patients with ischemic left ventricular dysfunction.

BACKGROUND: Bone-marrow derived endothelial progenitor cells (CD34+ and VEGFR2+ KDR+ EPC) and endothelial-derived microparticles (CD 31+Annexin V+, EMP; indicator for endothelial apoptosis) were examined in the peripheral blood of 35 male, clinically stable patients with 3-vessel coronary artery disease (CAD). The patients were divided in 2 groups, those with preserved or normal function (n = 17; EF 65 +/- 6%) and those with reduced left ventricular (LV) function (n = 18; EF 36 +/- 11%). METHODS AND RESULTS: The number of circulating EPCs was decreased by 25% (P = .07) and the number of EMPs was increased by 109 % (P < .05) in patients with LV dysfunction compared with those with normal or preserved LV function. EPCs were positively correlated (r = 0.24 for patients with LV dysfunction and r = 0.28 for patients with preserved LV function) with endothelial function as assessed by flow-mediated vasodilatation. In contrast, EMPs were inversely correlated (r = -0.42 for patients with LV dysfunction and r = -0.49 for patients with preserved LV function). CONCLUSIONS: CAD patients with significant LV dysfunction show an increased index of endothelial cell damage. This decrease (or lack of compensatory elevation) of EPCs may result in a reduced potential for repair and thus contribute at least in part to the pathogenesis of endothelial dysfunction.

The CYP2J2 G-50T polymorphism and myocardial infarction in patients with cardiovascular risk profile.

BACKGROUND: Cytochrome P450 (CYP) enzyme 2J2, an epoxygenase predominantly expressed in the heart, metabolizes arachidonic acid to biologically active eicosanoids. One of the CYP2J2 products, 11, 12-epoxyeicosatrienoic acid, has several vasoprotective effects. The CYP2J2-G-50T-promotor polymorphism decreases gene expression and is associated with coronary artery disease. This association supports the vascular protective role of CYP-derived eicosanoids in cardiovascular disease. In the present study, we investigated the influence of this polymorphism on survived myocardial infarction in two study groups of patients with on average high cardiovascular risk profile. METHODS: The CYP2J2 polymorphism was genotyped in two groups of patients that were collected with the same method of clinical data collection. Data from 512 patients with sleep apnoea (group: OSA) and on average high cardiovascular risk profile and from another 488 patients who were admitted for coronary angiography (CAR-group) were evaluated for a potential correlation of the CYP2J2 polymorphism G-50T and a history of myocardial infarction. The G-50T polymorphism of the CYP2J2 gene was genotyped by allele specific restriction and light cycler analysis. RESULTS: The T-allele of the polymorphism was found in 111 (11.1%; CAR-group: N = 65, 13.3%; OSA: N = 46, 9.0%). 146 patients had a history of myocardial infarction (CAR: N = 120, 24.6%; OSA: N = 26, 5.1%). Cardiovascular risk factors were equally distributed between the different genotypes of the CYP2J2 G-50T polymorphism. In the total group of 1000 individuals, carriers of the T-allele had significantly more myocardial infarctions compared to carriers of the wild type (T/T or G/T: 21.6%; G/G: 13.7%; p = 0.026, odds ratio 1.73, 95%-CI [1.06-2.83]). In the multivariate logistic regression analysis the odds ratio for a history of myocardial infarction in carriers of the T-allele was 1.611, 95%-CI [0.957-2.731] but this trend was not significant (p = 0.073). CONCLUSION: In presence of other risk factors, the CYP2J2 G-50T failed to show a significant role in the development of myocardial infarction. However, since our result is close to the border of significance, this question should be clarified in larger, prospective studies in the future.

Social Gradients in Myocardial Infarction and Stroke Diagnoses in Emergency Medicine.

BACKGROUND: Persons of lower socio-economic status are at higher risk of disease, especially with respect to severe and chronic illnesses. To date, there have not been any studies with large case numbers regarding acute medical emergencies in this population. METHODS: In a retrospective study, data were obtained on all cases treated by emergency physicians in Bochum, Germany, in 2014/2015, including the diagnoses that were made by the emergency physicians. There were a total of 16 767 cases. The local unemployment rate was taken as an indicator of the socioeconomic situation of a neighborhood; it was defined as the percentage of registered unemployed persons among persons aged 15 to 64 with their domicile in the neighborhood. 12 168 cases were grouped by emergency medical diagnosis and analyzed with respect to the three most heavily represented diagnostic categories (cardiovascular, neurological, and pulmonary emergencies), which accounted for nearly two-thirds of all diagnoses. RESULTS: The overall rates of deployment involving emergency physicians were found to be positively correlated with the unemployment rate. After adjustment for age, sex, and possible confounders, this correlation was statistically significant (p<0.01). The indirectly standardized rate ratio (IRR) for the overall case-activity rate ranged from 0.841 (95% confidence interval: [0.808; 0.875]) with less than 5% unemployment to 1.212 [1.168; 1.256] with 9.5% unemployment or higher. The same finding was obtained with respect to diagnosis-specific case activity in each of the three main diagnostic categories (cardiovascular, neurological, and pulmonary emergencies), as well as for the respective commonest individual diagnoses (acute coronary syndrome/circulatory arrest [1498 cases], transient ischemic attack/ischemic stroke/intracerebral hemorrhage [1274 cases], and asthma/chronic obstructive pulmonary disease [663 cases]). CONCLUSION: This study shows that the case-activity rate of the emergency medical services is significantly higher in socially disadvantaged neighborhoods, both with respect to total numbers and with respect to individual diseases. It demonstrates a problem affecting society as a whole, which should be taken into account in the organization of medical rescue services.

Risk factors and myocardial infarction in patients with obstructive sleep apnea: impact of beta2-adrenergic receptor polymorphisms.

BACKGROUND: The increased sympathetic nervous activity in patients with obstructive sleep apnea (OSA) is largely responsible for the high prevalence of arterial hypertension, and it is suggested to adversely affect triglyceride and high-density lipoprotein (HDL) cholesterol levels in these patients. The functionally relevant polymorphisms of the beta2-adrenergic receptor (Arg-47Cys/Arg16Gly and Gln27Glu) have been shown to exert modifying effects on these risk factors in previous studies, but results are inconsistent. METHODS: We investigated a group of 429 patients (55 +/- 10.7 years; 361 men, 68 women) with moderate to severe obstructive sleep apnea (apnea/hypopnea index (AHI) 29.1 +/- 23.1/h) and, on average, a high cardiovascular risk profile (body mass index 31.1 +/- 5.6, with hypertension in 60.1%, dyslipidemia in 49.2%, and diabetes in 17.2% of patients). We typed the beta2-adrenergic receptor polymorphisms and investigated the five most frequent haplotypes for their modifying effects on OSA-induced changes in blood pressure, heart rate, and lipid levels. The prevalence of cardiovascular risk factors and coronary heart disease (n = 55, 12.8%) and survived myocardial infarction (n = 27, 6.3%) were compared between the genotypes and haplotypes. RESULTS: Multivariate linear/logistic regressions revealed a significant and independent (from BMI, age, sex, presence of diabetes, use of antidiabetic, lipid-lowering, and antihypertensive medication) influence of AHI on daytime systolic and diastolic blood pressure, heart rate, prevalence of hypertension, and triglyceride and HDL levels. The beta2-adrenergic receptor genotypes and haplotypes showed no modifying effects on these relationships or on the prevalence of dyslipidemia, diabetes, and coronary heart disease, yet, for all three polymorphisms, heterozygous carriers had a significantly lower relative risk for myocardial infarction (Arg-47Cys: n = 195, odds ratio (OR) = 0.32, P = 0.012; Arg16Gly: n = 197, OR = 0.39, P = 0.031; Gln27Glu: OR = 0.37, P = 0.023). Carriers of the most frequent haplotype (n = 113) (haplotype 1; heterozygous for all three polymorphisms) showed a five-fold lower prevalence of survived myocardial infarction (OR = 0.21, P = 0.023). CONCLUSION: Our study showed no significant modifying effect of the functionally relevant beta2-adrenergic receptor polymorphisms on OSA-induced blood pressure, heart rate, or lipid changes. Nevertheless, heterozygosity of these polymorphisms is associated with a lower prevalence of survived myocardial infarction in this group with, on average, a high cardiovascular risk profile.

Asymmetric dimethylarginine is an independent risk factor for coronary heart disease: results from the multicenter Coronary Artery Risk Determination investigating the Influence of ADMA Concentration (CARDIAC) study.

BACKGROUND: Asymmetric dimethylarginine (ADMA) plasma levels have been shown to be elevated in diseases related to endothelial dysfunction such as hypertension, hyperlipidemia, diabetes mellitus, and others. It has been shown that ADMA predicts cardiovascular mortality in patients who have coronary heart disease (CHD). However, the question whether ADMA is an independent risk factor for CHD still remains unresolved. METHODS: The CARDIAC study is a multicenter case-control study, designed to detect differences in ADMA plasma levels between patients with CHD and controls from the general population. We included in our analysis 131 cases and 131 controls, matched for age, sex, and body mass index. RESULTS: We found that cases had higher ADMA plasma levels than controls (0.70 micromol/L [0.59-0.87 micromol/L] vs 0.60 micromol/L [0.54-0.69 micromol/L], P < .001). To evaluate the predictive power of ADMA regarding CHD, we calculated 2 multivariate logistic regression models including laboratory parameters and traditional risk factors. The odds ratio for ADMA in the multivariate model including the laboratory characteristics was 2.59 (1.61-4.17; P < .001); the odds ratio for the multivariate model including other risk factors was 6.04 (2.56-14.25; P < .001) for the third tertile (>0.72 micromol/L) versus the first (<0.58 micromol/L). CONCLUSIONS: We conclude from the results of our study that ADMA is an independent risk factor for CHD.

[Diagnosis and therapy of pulmonary embolism]. / Diagnose und Therapie der Lungenembolie.

Pulmonary embolism (PE) as a potentially life-threatening condition requires immediate medical intervention. Even the mere suspicion of a PE demands the initiation of a therapy with heparin. According to the patient's hemodynamic stability further diagnostic and therapeutic steps have to be taken. In case of a stable hemodynamic situation both the clinical probability of a PE and diagnostic imaging as well as the determination of D-dimers lead to the diagnosis. These patients should be anticoagulated with heparin. Unstable hemodynamic patients need to be monitored on the intensive care unit; echocardiography and, if needed, spiral computed tomography are the most important diagnostic tools. Due to this serious situation lung artery perfusion needs to be restituted by thrombolysis. Additionally, secondary prevention with vitamin K antagonists (INR [International Normalized Ratio] 2.0-3.0) is recommended depending on anamnesis and accordance to a risk group.

Dosimetric measurements in isolated human coronary arteries: comparison of commercially available iridium(192) with strontium/yttrium(90) emitters.

BACKGROUND: Intravascular brachytherapy is being applied more and more in patients with coronary artery disease for the prevention of restenosis subsequent to balloon angioplasty, in particular after stent implantation. Several radiation sources (beta- and gamma-emitters) are available in clinical routine. It was the purpose of this study to compare the radiation doses at the level of the adventitia in diseased and stented human coronary arteries for (192)Ir and (90)Sr/Y emitters in routine use. In contrast to previously published work, we performed dosimetry instead of calculating depth-dose distribution by use of the Monte Carlo system. METHODS AND RESULTS: Postmortem calcified human coronary artery segments were stented and placed in an organ bath. Commercially available gamma-emitters ((192)Ir; Cordis Checkmate) and beta-emitters ((90)Sr/Y; Novoste Beta-Cath) were used. Relative dose distributions along the adventitia were measured by a specially designed scintillation detector system. Whereas dose perturbations caused by stents and calcified plaque were negligible for the (192)Ir source, radiation from the beta source was significantly impaired (as much as 40%) at the level of the adventitia (3.0-mm vessel diameter). Dose perturbation was clearly dependent on the extent and severity of calcification, less affected by stent material. CONCLUSIONS: Dose perturbation caused by calcified plaque and metallic stents is significant for beta-sources. This dosimetric difference between beta- and gamma-emitters in diseased coronary arteries should be considered when calculating doses in intravascular brachytherapy.

Hospital-wide first-responder automated external defibrillator programme: 1 year experience.

The first year experience with a hospital-wide first-responder automated external defibrillator (AED) programme implemented in a 683-bed University Hospital is reported. Throughout the hospital, 14 "AED access spots" were identified which could be easily reached from all wards and diagnostic rooms within 30s. AEDs were installed (Lifepak 500; Medtronik PhysioControl Corp., Redmond, USA, equipped with a Biolog 3000i portable ECG monitor; Micromedical Industries Ltd., Labrador, Australia). Within 3 months, 120 medical officers, 750 nurses, and 50 administrative or technical staff underwent a 2h training programme. An AED was applied and activated by nurses/medical staff before the cardiac arrest team arrived in 27 of 33 cases (81.8%) of witnessed cardiac arrest. The median time from onset of the emergency call to the activation of the AED (record of ECG) was on average 2.1 min (range 1.0--4.5 min). In 18 of 27 cases in which the AED was installed promptly, the primary arrest rhythm was either VT or VF, and the AED delivered a shock. For this subgroup, the rate of return of spontaneous circulation and the rate of discharge at home were 88.9 and 55.6%, respectively. This encourages us to extend the concept of first-responder AED-defibrillation throughout our hospital.

Selective cyclo-oxygenase-2 inhibition with parecoxib acutely impairs endothelium-dependent vasodilatation in patients with essential hypertension.

BACKGROUND: Cyclo-oxygenase (COX)-2 isoform appears to be a major source of the vasodilator, prostacyclin. Both prostacyclin and nitric oxide may contribute to the regulation of vascular tone and endothelial-mediated homeostasis. OBJECTIVE: To evaluate the effects of acute COX-2 inhibition on endothelial function in the forearm circulation of patients with essential hypertension. METHODS: Forty patients with essential hypertension as the only risk factor were studied. Forearm blood flow was measured by venous occlusion phlethysmography. Vascular responses were measured after intra-arterial infusion of the endothelium-dependent agonist acetylcholine (15, 30, or 40 microg/min) and the endothelium-independent agonist nitroprusside (1.6, 3.2, or 4.0 microg/min). Patients were allocated randomly to groups to receive the non-selective COX-inhibitor, acetylsalicylate-lysin (500 mg intravenously), or the selective COX-2 inhibitor, parecoxib, an injectable prodrug of valdecoxib (20 mg intravenously). The infusion procedure was repeated 30 min later. RESULTS: Acetylcholine increased concentration-dependent forearm blood flow. This increase was significantly augmented by acetylsalicylate-lysin, but significantly diminished by parecoxib. Neither acetylsalicylate-lysin nor parecoxib modified the vasodilator responses to nitroprusside. CONCLUSION: COX-2 inhibition with the prodrug, parecoxib, diminishes the acetylcholine-induced vasodilatation in the forearm circulation of patients with essential hypertension. It is speculated that the production of vasodilator prostaglandins may be important in pathological states with endothelial dysfunction, at least in patients with essential hypertension.

Occlusion of pseudoaneurysms using human or bovine thrombin using contrast-enhanced ultrasound guidance.

Percutaneous thrombin occlusion of pseudoaneurysms complicating invasive coronary interventions has emerged as a useful therapeutic tool. To facilitate thrombin occlusion and make the procedure even more secure, preinjection of echo contrast medium during duplex ultrasound was tested in 132 patients. Complete and immediate occlusion of the pseudoaneurysm was achieved in 99.2% (131 of 132 patients). No complications related to the injection of thrombin were documented. Contrast-enhanced ultrasound-guided thrombin occlusion was a safe and effective therapeutic option. In aneurysms with complex morphology or multiple cavities, preinjection of contrast medium was helpful for documenting the flow pattern.