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.

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.

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.

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.

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.

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.

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.

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.

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.

Basic life support skills of high school students before and after cardiopulmonary resuscitation training: a longitudinal investigation.

BACKGROUND: Immediate bystander cardiopulmonary resuscitation (CPR) significantly improves survival after a sudden cardiopulmonary collapse. This study assessed the basic life support (BLS) knowledge and performance of high school students before and after CPR training. METHODS: This study included 132 teenagers (mean age 14.6 ± 1.4 years). Students completed a two-hour training course that provided theoretical background on sudden cardiac death (SCD) and a hands-on CPR tutorial. They were asked to perform BLS on a manikin to simulate an SCD scenario before the training. Afterwards, participants encountered the same scenario and completed a questionnaire for self-assessment of their pre- and post-training confidence. Four months later, we assessed the knowledge retention rate of the participants with a BLS performance score. RESULTS: Before the training, 29.5% of students performed chest compressions as compared to 99.2% post-training (P < 0.05). At the four-month follow-up, 99% of students still performed correct chest compressions. The overall improvement, assessed by the BLS performance score, was also statistically significant (median of 4 and 10 pre- and post-training, respectively, P < 0.05). After the training, 99.2% stated that they felt confident about performing CPR, as compared to 26.9% (P < 0.05) before the training. CONCLUSIONS: BLS training in high school seems highly effective considering the minimal amount of previous knowledge the students possess. We observed significant improvement and a good retention rate four months after training. Increasing the number of trained students may minimize the reluctance to conduct bystander CPR and increase the number of positive outcomes after sudden cardiopulmonary collapse.

A prospective, single-blind, multicenter, dose escalation study of intracoronary iNOS lipoplex (CAR-MP583) gene therapy for the prevention of restenosis in patients with de novo or restenotic coronary artery lesion (REGENT I extension).

Neointimal hyperplasia causing recurrent stenosis is a limitation of the clinical utility of percutaneous transluminal coronary interventions (PCI). Nitric oxide (NO) inhibits smooth muscle cell proliferation, platelet activation, and inflammatory responses, all of which have been implicated in the pathogenesis of restenosis. In animals, neointimal proliferation after balloon injury has been shown to be effectively reduced by gene transfer of the inducible NO synthase (iNOS). The primary objective of this first multicenter, prospective, single-blind, dose escalation study was to obtain safety and tolerability information of the iNOS lipoplex (CAR-MP583) gene therapy for reducing restenosis following PCI. Local coronary intramural CAR-MP583 delivery was achieved using the Infiltrator balloon catheter. A total of 30 patients were treated in the study (six patients, 0.5 µg; six patients, 2.0 µg; six patients, 5.0 µg; and 12 patients, 10 µg). There were no complications related to local application of CAR-MP583. In one patient, PCI procedure-related transient vessel occlusion occurred with consecutive troponin elevation. There were no signs of inflammatory responses or hepatic or renal toxicity. No dose relationship was seen with regard to adverse events across the dose groups. Thus, coronary intramural lipoplex-enhanced iNOS gene therapy during PCI is feasible and appears to be safe. These initial clinical results are encouraging to support further clinical research, in particular in conjunction with new local drug delivery technologies.

[In-hospital resuscitation concept with first-responder defibrillation. 2-year experience]. / Innerklinisches notfallmanagement mit "first-responder"-reanimation : 2-jahres-erfahrung.

BACKGROUND AND PURPOSE: Sudden cardiac arrest appears in 1-5 patients/ 1,000 clinical admissions. In spite of different research approaches, the prognosis after in-hospital resuscitation has not significantly improved in the last 40 years. This account presents the experiences with a hospital-wide emergency plan using the concept of defibrillation by first responders. METHODS: In 2003, a hospital-wide emergency plan was implemented. The concept comprised the setup of 15 "defibrillator points", training of the entire hospital personnel as first responder, and the introduction of an emergency team. Over the following 3 years, the concept was optimized. In a period from May 2006 to April 2008, the data of all patients who received an in-hospital resuscitation were collected. RESULTS: Within 24 months, a total of 41 resuscitations were conducted. Out of these, 24 patients (58%) were under intensive monitoring when the event occurred. Initially, 15 patients (36%) showed ventricular fibrillation, 15 (36%) a pulseless electrical activity, and eleven (27%) an asystoly. A total of twelve patients (29%) left hospital alive. About half of them (42%) experienced ventricular fibrillation and were under observation at the time of event. CONCLUSION: The data collected since the implementation of the hospital- wide emergency plan in 2003 reflect the daily clinical routine. The results show that there is a better outcome especially in patients with ventricular fibrillation when receiving first-responder defibrillation.

A first city-wide early defibrillation project in a German city: 5-year results of the Bochum against sudden cardiac arrest study.

BACKGROUND: Immediate defibrillation is the decisive determinant of prognosis in patients suffering from cardiac/circulatory arrest caused by ventricular fibrillation (VF). Therefore, various national and international associations recommend that first responders use defibrillators as soon as possible and also recommend public access to early defibrillation programmes. Here we report the results of the first city-wide early defibrillation project in a large German urban area. METHODS: There were 155 automated external defibrillators (AEDs) put into operation in the Bochum municipal area, and 6,294 people took part in cardiopulmonary resuscitation (CPR) and AED training. Free, accessible AEDs were installed in places with large volumes of people. Additionally, emergency forces were progressively equipped with AEDs. RESULTS: Twelve AED administrations prior to the arrival of an emergency physician were recorded and analysed over a period of 5 years (08/2004-08/2009). Rhythm analysis via AED demonstrated VF in seven cases, non-malignant dysrhythmias in four cases and asystole in one case. Two of the seven patients with VF were successfully defibrillated and survived cardiac/circulatory arrest without any neurological sequelae. Eight of the 12 AED applications were performed by laymen. The mean time between switching the unit on and applying the electrodes to the patient was 39 seconds (SD +/-20 sec). On average, another 20 seconds elapsed before the AED recommendation of "shock delivery" was displayed, and a total of 96 seconds elapsed before shock administration (+/- 56 sec). CONCLUSION: Consistent with other reports, our findings show that the organisation of a city-wide initiative by a project office combining public access and first-responder defibrillation programmes can be safe, feasible and successful. Our experiences confirm that strategic planning of AED placement is a prerequisite for successful, cost-effective resuscitation.

Unrecognized secondary causes of hypertension in patients with hypertensive urgency/emergency: prevalence and co-prevalence.

BACKGROUND: Hypertensive urgency/emergency occurs frequently, yet no prospective data on common secondary causes, including sleep apnea (SA), renal artery stenosis (RAS), and hyperaldosteronism, are available. METHODS: Patients presenting to the emergency room for over 1 year with systolic blood pressure > or =180 mmHg and/or diastolic blood pressure > or =100 mmHg and typical symptoms were included. RAS was diagnosed by direct duplex/Doppler ultrasound of the renal artery, resistance index, and imaging. The aldosterone/renin ratio (ARR) was determined from morning blood samples taken with the patients supine after > or =2 h of rest. A positive ARR (>50) was followed by saline infusion to exclude primary hyperaldosteronism. SA was evaluated by nasal breathing flow screening; when positive [apnea/hypopnea index (AHI) >5/h], complete polysomnography was performed. RESULTS: Of 161 patients (age, 66.0 +/- 13.1 years; BMI, 28.6 +/- 5.1 kg), 131 had previously identified hypertension (duration, 12.7 +/- 11.5 years; 1.9 +/- 1.5 antihypertensive medications). SA was found in 114 (70.8%) patients [18% mild (AHI: 5-15/h), 26.8% moderate (15.1-30/h), and 24.2% severe (>30/h)]. Aldosterone levels exceeded 160 pg/ml in 22 of 23 patients with hyperaldosteronism; 4 had primary and 12 had secondary hyperaldosteronism. Thirteen (8.1%) patients had RAS. Three secondary causes were found in 1 patient (0.6%), > or =2 in 25 (15.5%), and > or =1 in 124 patients (77.0%). Of 150 detected secondary causes, only 5 were recognized previously. CONCLUSIONS: Secondary causes of hypertension are common and predominantly unrecognized in patients with hypertensive urgency/emergency. Co-prevalence of secondary causes occurs in about 15% and should be considered before therapeutic intervention.

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.

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.

Hormonal status modulates circulating endothelial progenitor cells.

OBJECTIVE: Endothelial progenitor cells (EPCs) may have an important role in vascular homeostasis and repair. METHODS: We examined the level of circulating EPCs in pre- (n = 22; mean age 28.7 years), and postmenopausal healthy females without (n = 30; mean age 61.6 years) or under current hormone replacement therapy (HRT) (n = 19; mean age 59.8 years). RESULTS: Premenopausal females had the highest level of circulating EPCs (0.147 +/- 0.076 per thousand of polymorphnuclear cells). The level of EPCs was lowest in postmenopausal females (0.094 +/- 0.058 per thousand), and increased significantly with HRT on average by 25.5%. In addition, the proliferative capacity of circulating EPCs was assessed under cell culture conditions. This capacity was significantly increased in EPCs isolated from postmenopausal subjects under current HRT as compared to corresponding samples obtained from postmenopausal females without HRT. CONCLUSIONS: This observation is in line with the hypothesis that the hormonal status in females modulates the cardiovascular risk and that circulating EPCs could be involved in this phenomenon.

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.