Results from the "Me & My Heart" (eMocial) Study: a Randomized Evaluation of a New Smartphone-Based Support Tool to Increase Therapy Adherence of Patients with Acute Coronary Syndrome.

PURPOSE: This study evaluated whether patient support, administered via an electronic device-based app, increased adherence to treatment and lifestyle changes in patients with acute coronary syndrome (ACS) treated with ticagrelor in routine clinical practice. METHODS: Patients (aged ≥ 18 years) with diagnosed ACS treated with ticagrelor co-administered with low-dose acetylsalicylic acid were randomized into an active group (with support tool app for medication intake reminders and motivational messages) and a control group (without support tool app), and observed for 48 weeks (ClinicalTrials.gov Identifier: NCT02615704). Patients were asked to complete the 36-item Short-Form Health Survey (SF-36) and Lifestyle Changes Questionnaire (LSQ), and were assessed for blood pressure and body mass index (BMI) at baseline (visit 1) and at the end of the study (visit 2). Medication adherence was measured using the Brilique Adherence Questionnaire (BAQ). RESULTS: Patients (N = 676) were randomized to an active (n = 342) or a control (n = 334) group. BAQ data were available for 174 patients in the active group and 174 patients in the control group. Over the 48-week period, mean (standard deviation) adherence for the active and control groups was 96.4% (13.2%) and 91.5% (23.1%), respectively (effect of app intervention, p < 0.05). There were no significant differences in blood pressure and BMI between visits. General improvements in SF-36 and LSQ scores were observed for both groups. CONCLUSION: The patient support tool app was associated with significant improvements in patient-reported treatment adherence compared with a data collection app alone in patients prescribed ticagrelor for ACS.

Comparing routine administrative data with registry data for assessing quality of hospital care in patients with myocardial infarction using deterministic record linkage.

BACKGROUND: Assessment of quality of care in patients with myocardial infarction (MI) should be based on data that effectively enable determination of quality. With the need to simplify measurement techniques, the question arises whether routine data can be used for this purpose. We therefore compared data from a German sickness fund (AOK) with data from the Berlin Myocardial Infarction Registry (BMIR). METHODS: We included patients hospitalised for treatment of MI in Berlin from 2009-2011. We matched 2305 patients from AOK and BMIR by using deterministic record linkage with indirect identifiers. For matched patients we compared the frequency in documentation between AOK and BMIR for quality assurance variables and calculated the kappa coefficient (KC) as a measure of agreement. RESULTS: There was almost perfect agreement in documentation between AOK and BMIR data for matched patients for: catheter laboratory (KC: 0.874), ST elevation MI (KC: 0.826), diabetes (KC: 0.818), percutaneous coronary intervention (KC: 0.860) and hospital mortality (KC: 0.952). The remaining variables compared showed moderate or less than moderate agreement (KC < 0.6), and were grouped in Category II with less frequent documentation in AOK for risk factors and aspects of patients' history; in Category III with more frequent documentation in AOK for comorbidities; and in Category IV for medication at and after hospital discharge. CONCLUSIONS: Routine data are primarily collected and defined for reimbursement purposes. Quality assurance represents merely a secondary use. This explains why only a limited number of variables showed almost perfect agreement in documentation between AOK and BMIR. If routine data are to be used for quality assessment, they must be constantly monitored and further developed for this new application. Furthermore, routine data should be complemented with registry data by well-established methods of record linkage to realistically reflect the situation - also for those quality-associated variables not collected in routine data.

The Post-Myocardial Infarction Pacing Remodeling Prevention Therapy (PRomPT) Trial: Design and Rationale.

BACKGROUND: Despite considerable improvements in the medical management of patients with myocardial infarction (MI), patients with large MI still have substantial risk of developing heart failure. In the early post-MI setting, implantable cardioverter defibrillators have reduced arrhythmic deaths but have no impact on overall mortality. Therefore, additional interventions are required to further reduce the overall morbidity and mortality of patients with large MI. METHODS: The Pacing Remodeling Prevention Therapy (PRomPT) trial is designed to study the effects of peri-infarct pacing in preventing adverse post-MI remodeling. Up to 120 subjects with peak creatine phosphokinase >3,000 U/L (or troponin T >10 µg/L) at time of MI will be randomized to either dual-site or single-site biventricular pacing with the left ventricular lead implanted in a peri-infarct region or to a nonimplanted control group. Those randomized to a device will be blinded to the pacing mode, but randomization to a device or control cannot be blinded. Subjects randomized to pacing will have the device implanted within 10 days of MI. The primary objective is to assess the change in left ventricular end-diastolic volume from baseline to 18 months. Secondary objectives are to assess changes in clinical and mechanistic parameters between the groups, including rates of hospitalization for heart failure and cardiovascular events, the incidence of sudden cardiac death and all-cause mortality, New York Heart Association functional class, 6-minute walking distance, and quality of life. CONCLUSIONS: The PRomPT trial will provide important evidence regarding the potential of peri-infarct pacing to interrupt adverse remodeling in patients with large MI.

Implementation of the ESC STEMI guidelines in female and elderly patients over a 20-year period in a large German registry.

AIMS: We investigated the implementation of new guidelines in ST-segment elevation myocardial infarction (STEMI) patients in a large real-world patient population in the metropolitan area of Berlin (Germany) over a 20-year period. METHODS: From January 2000 to December 2019, a total of 25 792 patients were admitted with STEMI to one of the 34 member hospitals of the Berlin-Brandenburg Myocardial Infarction Registry (B2HIR) and were stratified for sex and age < 75 and ≥ 75 years. RESULTS: The median age of women was 72 years (IQR 61-81) compared to 61 years in men (IQR 51-71). PCI treatment as a standard of care was implemented in men earlier than in women across all age groups. It took two years from the 2017 class IA ESC STEMI guideline recommendation to prefer the radial access route rather than femoral until > 60% of patients were treated accordingly. In 2019, less than 60% of elderly women were treated via a radial access. While the majority of patients < 75 years already received ticagrelor or prasugrel as antiplatelet agent in the year of the class IA ESC STEMI guideline recommendation in 2012, men ≥ 75 years lagged two years and women ≥ 75 three years behind. Amongst the elderly, in-hospital mortality was 22.6% (737) for women and 17.3% (523) for men (p < 0.001). In patients < 75 years fatal outcome was less likely with 7.2% (305) in women and 5.8% (833) in men (p < 0.001). After adjustment for confounding variables, female sex was an independent predictor of in-hospital mortality in patients ≥ 75 years (OR 1.37, 95% CI 1.12-1.68, p = 0.002), but not in patients < 75 years (p = 0.076). CONCLUSION: In-hospital mortality differs considerably by age and sex and remains highest in elderly patients and in particular in elderly females. In these patient groups, guideline recommended therapies were implemented with a significant delay.

Changes in treatment for NSTEMI in women and the elderly over the past 16 years in a large real-world population.

AIMS: This study investigates the changes in therapy for Non-ST-Elevation Myocardial Infarction (NSTEMI) over the past 16 years in a large German registry. In particular, the high-risk population of female and elderly patients was analyzed. METHODS: In total, 19.383 patients presenting with NSTEMI were included in this study. Patients were stratified by age groups <75 years and ≥75 years and by sex. Four different time periods from 2000-2004, 2005-2008, 2009-2012 and 2013-2016 were compared. Influence on hospital mortality as the primary outcome measure was assessed by logistic regression analysis. Secondary outcome measures included percutaneous coronary intervention (PCI), the use of drug eluting stents (DES), radial access route and major adverse cardiovascular events (MACE), defined as all-cause mortality, stroke, re-infarction, percutaneous re-intervention, intervention-related bleeding, cardiopulmonary resuscitation and new onset of cardiogenic shock or need for mechanical ventilation. RESULTS: Mortality decreased in all age groups between the initial time period and the most recent one (8.9% vs. 4.5%, p < 0.01), particularly in female patients ≥75 years (18.2% in 2000-2004 vs. 7.9% in 2013-2016, p < 0.01). Revascularization rates differed by gender (68.3% in women vs. 78.1% in men, p < 0.01) and by age (64.2% for ≥75 years vs. 80.9% for <75 years, p < 0.01). PCI rates in elderly female patients increased from 28.7% to 69.8% (p < 0.01) from the initial to the latest period. CONCLUSIONS: The present study demonstrates, that revascularization rates improved in all patient groups over the study period. However, females and elderly patients still remain less likely to be treated according to current guidelines.

Bi-level positive pressure ventilation and adaptive servo ventilation in patients with heart failure and Cheyne-Stokes respiration.

OBJECTIVES: Nocturnal positive pressure ventilation (PPV) has been shown to be effective in patients with impaired left ventricular ejection fraction (LVEF) and Cheyne-Stokes respiration (CSR). We investigated the effect of a bi-level PPV and adaptive servo ventilation on LVEF, CSR, and quantitative sleep quality. METHODS: Thirty-seven patients (New York heart association [NYHA] II-III) with LVEF<45% and CSR were investigated by electrocardiography (ECG), echocardiography and polysomnography. The CSR index (CSRI) was 32.3+/-16.2/h. Patients were randomly treated with bi-level PPV using the standard spontaneous/timed (S/T) mode or with adaptive servo ventilation mode (AutoSetCS). After 6 weeks, 30 patients underwent control investigations with ECG, echocardiography, and polysomnography. RESULTS: The CSRI decreased significantly to 13.6+/-13.4/h. LVEF increased significantly after 6 weeks of ventilation (from 25.1+/-8.5 to 28.8+/-9.8%, p<0.01). The number of respiratory-related arousals decreased significantly. Other quantitative sleep parameters did not change. The Epworth sleepiness score improved slightly. Daytime blood pressure and heart rate did not change. There were some differences between bi-level PPV and adaptive servo ventilation: the CSRI decreased more in the AutoSetCS group while the LVEF increased more in the bi-level PPV group. CONCLUSIONS: Administration of PPV can successfully attenuate CSA. Reduced CSA may be associated with improved LVEF; however, this may depend on the mode of PPV. Changed LVEF is evident even in the absence of significant changes in blood pressure.

Nocturnal overdrive pacing for the treatment of sleep apnea syndrome.

STUDY OBJECTIVES: We investigated the effect of 1 week of nocturnal overdrive pacing (NOP) on the apnea-hypopnea index (AHI) in patients with a chronically implanted pacemaker and diagnosed during a screening phase with sleep apnea. DESIGN: Randomized, single-blind, crossover study. SETTING: University medical centers in Zürich, Switzerland, and Berlin, Germany. PATIENTS: Nineteen patients with mild to severe sleep apnea/hypopnea (16 men, mean age = 68.8 +/- 11.4 years) participated. The individuals did not suffer from permanent atrial arrhythmia, did not use continuous positive airway pressure, and had been implanted with atrial or dual-chamber pacemakers. INTERVENTIONS: Nocturnal lower rates were 45 and 75 beats per minute (bpm) at night for the control and NOP arms, respectively, and daytime lower rates were 60 bpm. Subjects were in each arm for 1 week. MEASUREMENTS AND RESULTS: Heart-rate increase from control (61 +/- 9 bpm) to NOP (78 +/- 4 bpm) followed by significant reduction in circulation time (24.6 seconds control, 20.7 seconds NOP; p = .04) resulted in no significant change in AHI (26.8 +/- 17.1/h control, 23.0 +/- 16.7/h NOP; p = .49). Seven subjects characterized by a higher hypopnea index, less stage 1 and 2 sleep, and less slow-wave sleep improved at least 1 AHI severity level with NOP, mainly attributable to reduction of hypopneas. CONCLUSION: NOP over a period of 1 week followed by a reduction in circulation time did not improve AHI in patients with SA. Whether an improvement by 1 AHI severity level in a specific subset of patients reflects a true response remains to be elucidated by further studies.

Does diabetes mellitus explain the higher hospital mortality of women with acute myocardial infarction? Results from the Berlin Myocardial Infarction Registry.

BACKGROUND: Women with acute myocardial infarction (AMI) exhibit greater hospital mortality than do men. In general, diabetes mellitus is one of the major factors influencing the outcome of patients with AMI. The aim of this study was to analyze the interaction between diabetes and gender, specifically with regard to the higher hospital mortality of female AMI patients aged < or = 75 years. METHODS: We prospectively collected data from 3,715 patients aged < or = 75 (2,794 men, 921 women) with acute myocardial infarction who were treated in 25 hospitals in Berlin, Germany, from 1999 to 2002. In a multivariate analysis, we specifically studied the interaction between the factors diabetes mellitus and gender in their effects on hospital mortality. RESULTS: After adjustment in multivariate analysis, the interaction between gender and diabetes was statistically significant, and the estimated odds ratios were as follows: female diabetic patients compared with male diabetic patients, odds ratio (OR) = 2.28 (95% confidence interval [CI] 1.42-3.68); female diabetic patients compared with male nondiabetic patients, OR = 2.90 (95% CI 1.90-4.42); and female diabetic patients compared with female nondiabetic patients, OR = 2.92 (95% CI 1.75-4.87). There was no statistically significant difference between the risk of dying for female nondiabetic patients or for male diabetic patients when compared with male nondiabetic patients. CONCLUSIONS: In AMI patients aged < or = 75 years, female gender alone is not an independent predictor of hospital mortality. Detailed, multivariate analysis reveals that specifically diabetic women demonstrate higher hospital mortality than do men. Special attention should be provided to these female diabetic patients.

The Emergency Medical Care of Patients With Acute Myocardial Infarction.

BACKGROUND: Optimizing the emergency medical care chain might shorten the time to treatment of patients with ST-elevation myocardial infarction (STEMI). The initial care by a physician, and, in particular, correct ECG interpretation, are critically important factors. METHODS: From 1999 onward, data on the care of patients with myocardial infarction have been recorded and analyzed in the Berlin Myocardial Infarction Registry. In the First Medical Contact Study, data on initial emergency medical care were obtained on 1038 patients who had been initially treated by emergency physicians in 2012. Their pre-hospital ECGs were re-evaluated in a blinded fashion according to the criteria of the European Society of Cardiology. RESULTS: The retrospective re-evaluation of pre-hospital ECGs revealed that 756 of the 1038 patients had sustained a STEMI. The emergency physicians had correctly diagnosed STEMI in 472 patients (62.4%), and they had correctly diagnosed ventricular fibrillation in 85 patients (11.2%); in 199 patients (26.3%), the ECG interpretation was unclear. The pre-hospital ECG interpretation was significantly associated with the site of initial hospitalization and the ensuing times to treatment. In particular, the time from hospital admission to cardiac catheterization was longer in patients with an unclear initial ECG interpretation than in those with correctly diagnosed STEMI (121 [54; 705] vs. 36 [19; 60] minutes, p <0.001). After multivariate adjustment, this corresponded to a hazard ratio* of 2.67 [2.21; 3.24]. CONCLUSION: Pre-hospital ECG interpretation in patients with STEMI was a trigger factor with a major influence on the time to treatment in the hospital. The considerable percentage of pre-hospital ECGs whose interpretation was unclear implies that there is much room for improvement.

Determining the Feasibility of Spinal Cord Neuromodulation for the Treatment of Chronic Systolic Heart Failure: The DEFEAT-HF Study.

OBJECTIVES: The primary objective of the study was a change in left ventricular end-systolic volume index (LVESVi) from baseline to 6 months of spinal cord stimulation (SCS) therapy in the treatment arm compared to the control arm as measured by echocardiography. Secondary objectives were changes in peak oxygen uptake and N-terminal pro-B-type natriuretic peptide (NT-proBNP) between the treatment arm and control arm from baseline through 6 months. BACKGROUND: Abnormal neurohormonal activation is often responsible for progression of heart failure (HF). Treatment has often included drug therapy to modulate the neurohormonal axis. The purpose of the DEFEAT-HF (Determining the Feasibility of Spinal Cord Neuromodulation for the Treatment of Chronic Heart Failure) clinical study was to evaluate whether direct modulation of the nervous system through SCS improved HF metrics, including heart size, biomarkers, functional capacity, and symptoms. METHODS: The DEFEAT-HF study was a prospective, multicenter randomized (3:2), parallel, single-blind, controlled study to investigate whether SCS was a feasible therapy for the treatment of systolic HF for patients with New York Heart Association functional class III HF, left ventricular ejection fraction (LVEF) ≤35%, QRS duration <120 ms, and left ventricular end-diastolic dimension ≥55 mm. The primary objective of the DEFEAT-HF study was to evaluate the reduction in LVESVi after 6 months of SCS therapy in the treatment arm compared to the control arm. RESULTS: In total, 81 patients were enrolled, with 66 successfully randomized and implanted with the SCS device system. Seventy-six percent (50 of 66) had an implantable cardioverter-defibrillator at the baseline visit. Among randomized patients, the mean age was 61 years, 79% were male, mean LVEF was 27%, and mean QRS duration was 105 ms. The change in LVESVi over 6 months was not significantly different between randomization arms (SCS OFF: -2.2 [95% confidence interval: -9.1 to 4.6] vs. SCS ON: 2.1 [95% confidence interval: -2.7 to 6.9]; p = 0.30). Analyses of secondary endpoints for the study were also not significantly different. CONCLUSIONS: The present study does not provide evidence to support a meaningful change in clinical outcomes for HF patients receiving SCS. (Determining the Feasibility of Spinal Cord Neuromodulation for the Treatment of Chronic Heart Failure [DEFEAT-HF]; NCT01112579).

Cardiac fibroblasts and the mechano-electric feedback mechanism in healthy and diseased hearts.

Cardiac arrhythmia is a serious clinical condition, which is frequently associated with abnormalities of mechanical loading and changes in wall tension of the heart. Recent novel findings suggest that fibroblasts may function as mechano-electric transducers in healthy and diseased hearts. Cardiac fibroblasts are electrically non-excitable cells that respond to spontaneous contractions of the myocardium with rhythmical changes of their resting membrane potential. This phenomenon is referred to as mechanically induced potential (MIP) and has been implicated in the mechano-electric feedback mechanism of the heart. Mechano-electric feedback is thought to adjust the frequency of spontaneous myocardial contractions to changes in wall tension, which may result from variable filling pressure. Electrophysiological recordings of single atrial fibroblasts indicate that mechanical compression of the cells may activate a non-selective cation conductance leading to depolarisation of the membrane potential. Reduced amplitudes of MIPs due to pharmacological disruption of F-actin and tubulin suggest a role for the cytoskeleton in the mechano-electric signal transduction process. Enhanced sensitivity of the membrane potential of the fibroblasts to mechanical stretch after myocardial infarction correlates with depression of heart rates. It is assumed that altered electrical function of cardiac fibroblasts may contribute to the increased risk of post-infarct arrhythmia.

The Wilms' tumor suppressor Wt1 is expressed in the coronary vasculature after myocardial infarction.

Expression of the Wilms' tumor gene Wt1 in the epicardium is critical for normal heart development. Mouse embryos with inactivated Wt1 gene have extremely thin ventricles, which can result in heart failure and death. Here, we demonstrate that Wt1 can be activated in adult hearts by local ischemia. Wt1 mRNA was increased more than twofold in the left ventricular myocardium of rats between 1 day and 9 wk after infarction. Wt1 expression was localized by means of mRNA in situ hybridization and immunohistochemistry to vascular endothelial and vascular smooth muscle cells in the border zone of the infarcted tissue. A strikingly similar distribution was seen for vascular endothelial growth factor and two different cell proliferation markers in the coronary vessels of the ischemic heart. No Wt1 could be detected in the vasculature of the noninfarcted right ventricles. Wt1 expression in the coronary vessels of the ischemic heart was mimicked by exposure of rats to normobaric hypoxia (8% O2) and 0.1% CO, respectively. These findings demonstrate that Wt1 is expressed in the vasculature of the heart in response to local ischemia and hypoxia. They suggest that Wt1 has a role in the growth of coronary vessels after myocardial infarction.

Oxygen-regulated expression of the Wilms' tumor suppressor Wt1 involves hypoxia-inducible factor-1 (HIF-1).

The Wilms' tumor gene Wt1 is unique among tumor suppressors because of its requirement for the development of certain organs. We recently described de novo expression of Wt1 in myocardial blood vessels of ischemic rat hearts. The purpose of this study was to analyze the mechanism(s) of hypoxic/ischemic induction of Wt1. We show here that Wt1 mRNA and protein is up-regulated in the heart and kidneys of rats exposed to normobaric hypoxia (8% O2). Ectopic Wt1 immunoreactivity was detected in renal tubules of hypoxic rats, which also expressed the antiapoptotic protein Bcl-2 and contained significantly fewer TUNEL-positive cells than in normoxic kidneys. Wt1 expression was enhanced in the osteosarcoma line U-2OS and in Reh lymphoblast cells that were grown either at 1% O2 or in the presence of CoCl2 and desferrioxamine, respectively. The promoter of the Wt1 gene was capable of mediating expression of a luciferase reporter in response to hypoxia. We identified a hypoxia-responsive element in the Wt1 sequence that bound to hypoxia-inducible factor-1 (HIF-1) and was required for activation of the Wt1 promoter by CoCl2 and HIF-1. These findings demonstrate that Wt1 expression can be stimulated by hypoxia, which involves activation of the Wt1 promoter by HIF-1.

The Wilms' tumor suppressor Wt1 encodes a transcriptional activator of the class IV POU-domain factor Pou4f2 (Brn-3b).

The Wilms' tumor gene Wt1 encodes a zinc finger protein, which is required for normal formation of the genitourinary system and mesothelial tissues. Our recent findings indicate that Wt1 also plays a critical role in the development of ganglion cells in the vertebrate retina. Here we show that the POU-domain factor Pou4f2 (formerly Brn-3b), which is necessary for retinal ganglion cell survival, is up-regulated in human embryonic kidney (HEK)293 cells with stable Wt1 expression. Consistent with our previous observations of increased Pou4f2 mRNA in stably Wt1-transfeced HEK293 cells [EMBO J. 21 (2002) 1398], endogenous Pou4f2 was also elevated at the protein level in the HEK293 transfectants as well as in U2OS osteosarcoma cells that expressed an inducible Wt1 isoform. Transient co-transfection of a Wt1 expression construct activated a Pou4f2 promoter-reporter construct approximately 4-fold. Stimulation of the Pou4f2 promoter required a Wt1 binding element that was similar to a degenerative consensus site previously identified in other Wt1 responsive genes. Double-immunofluorescent labeling revealed co-expression of Pou4f2 and Wt1 in glomerular podocytes of adult kidney and in developing retinal ganglion cells of mouse embryos. Pou4f2 immunoreactivity was absent from the retinas of Wt1(-/-) embryos. In conclusion, we identified Pou4f2 as a novel downstream target gene of Wt1. Co-localization of both proteins in glomerular podocytes of the kidney and in developing retinal ganglion cells suggests a role for Wt1-Pou4f2 interaction in these tissues.

Effects of positive-pressure ventilation on the spontaneous baroreflex in healthy subjects.

To determine the short-term effects of noninvasive positive-pressure ventilation (PPV) on spontaneous baroreflex sensitivity, we acquired time series of R-R interval and beat-to-beat blood pressure in 55 healthy volunteers (mean age 46.5 +/- 10.5 yr) who performed breathing on four occasions at frequencies of 12 and 15 breaths/min without positive pressure (control) and also using PPV of 5 mbar. By using spectral and cross-spectral analysis, R-R interval variability and systolic blood pressure variability as well as the gain (alpha-index) of the baroreceptor reflex were estimated for the low-frequency and high-frequency (HF) bands. Compared with control breathing, PPV at 12 breaths/min and 15 breaths/min led to an increase in mean R-R (P < 0.001) and blood pressure (P < 0.05). The alpha-index of the HF band increased significantly for both respiratory frequencies (P < 0.05) due to PPV. These results indicate that short-term administration of PPV in normal subjects elicits a significant enhancement in the HF index of the baroreflex gain. These findings may contribute to understanding the mechanisms, indications, and effectiveness of positive pressure breathing strategies in treating cardiorespiratory and other disease conditions.

Antithrombotic therapy in patients with atrial fibrillation and acute coronary syndrome in the real world: Data from the Berlin AFibACS Registry.

BACKGROUND: Guidelines for the management of atrial fibrillation (AFib) recommend antithromboembolic treatment strategies for patients with AFib and acute coronary syndrome (AFibACS). Our study assessed how current guidelines are implemented in the metropolitan area of Berlin and which therapeutic options were chosen in light of stroke and bleeding riskin everyday practice. METHODS AND RESULTS: Between April 2008 and January 2012, we included 1,295 AFibACS patients in the AFibACS Registry, as part of the Berlin Myocardial Infarction Registry. Meanage of the patients was 76 years with numerous comorbidities (15.4% former stroke, 35.0% renal failure, 43.5% diabetes, 92.8% hypertension). Of all the patients, 888 were treated with stent implantation, 91 with balloon angioplasty, and 316 conservatively. Overall mortality was 11.6%, and 8.3% in stented patients. At hospital discharge, triple therapy was administered to 49.9% of stented cases. After adjustment, odds of receiving triple therapy were lower within creasing age and renal failure. Odds were higher after stent implantation, with a higher CHA2DS2-VASc score, and with any AFib category compared to initially diagnosed AFib. Between 2008 and 2011, triple therapy increased from 33.3% to 49.8% for stented patients and did not change significantly for those treated conservatively or with balloon angioplasty. CONCLUSIONS: These data suggest that in AFibACS patients, antithrombotic treatment focused on dual antiplatelet therapy for ACS, rather than on anticoagulation therapy for stroke prevention. Factors influencing therapy at discharge were age, renal failure, stent implantation, AFib category, and CHA2DS2-VASc score. During the study period, triple therapy increased for stented patients.

Routine early invasive strategy and in-hospital mortality in women with non-ST-elevation myocardial infarction: results from the Berlin Myocardial Infarction Registry (BMIR).

BACKGROUND: It is under discussion whether female patients with non-ST-elevation myocardial infarction (NSTEMI) benefit from routine invasive treatment strategy. We accordingly applied our data from the Berlin Myocardial Infarction Registry (BMIR) to analyze the association between early percutaneous coronary intervention (PCI) and hospital mortality in NSTEMI patients. METHODS: Data prospectively collected in the BMIR between 2004 and 2008 from 2808 patients (m=1820/w=988) directly admitted to hospitals with 24-h PCI facilities were included in the analysis. After adjustment for confounding variables, we compared in-hospital mortality for patients of both sexes with vs. without early PCI. RESULTS: Women with NSTEMI were, on average, 7years older than men and demonstrated significantly more comorbidities. A GPIIb/IIIa antagonist was applied in women less often than in men (31.4% vs. 38.4%, p=0.001), and an early PCI was also performed less often in women than in men (64.0% vs. 76.2%, p<0.001). In-hospital mortality was higher in women than in men (5.4% vs. 3.6%, p=0.027). In female patients with NSTEMI, after adjustment for differences in patients' characteristics, hospital mortality did not differ between those treated with early PCI and those managed conservatively (OR: 1.24, 95% CI 0.53-2.91). In contrast, hospital mortality in male patients was lower in those treated with an early PCI (OR: 0.41, 95% CI 0.21-0.78). CONCLUSION: In our clinical registry, early PCI in female patients with NSTEMI was not associated with lower hospital mortality. Further randomized-controlled trials are needed to better understand which women may benefit from early invasive therapy, and under which conditions such benefits are possible.

Enhanced L-type calcium currents in cardiomyocytes from transgenic rats overexpressing SERCA2a.

BACKGROUND: Previous research reported that transgenic rats overexpressing the sarco(endo)plasmic reticulum Ca(2+)-ATPase SERCA2a exhibit improved contractile function of the myocardium. Furthermore, impaired Ca(2+) uptake and reduced relaxation rates in rats with diabetic cardiomyopathy were partially rescued by transgenic expression of SERCA2a in the heart. OBJECTIVE: To explore whether enhanced Ca(2+) cycling in the cardiomyocytes of SERCA2a transgenic rats is associated with changes in L-type Ca(2+) (I(Ca-L)) currents. METHODS: The patch-clamp technique was used to measure whole-cell currents in cardiomyocytes from transgenic rats overexpressing SERCA2a and from wild-type (nontransgenic) animals. RESULTS: The amplitudes of I(Ca-L) currents at depolarizing pulses ranging from -45 mV to 0 mV (350 ms duration, 1 Hz) were significantly higher in cardiomyocytes of SERCA2a transgenic rats than in nontransgenic rats (1985±48 pA [n=32] versus 1612±55 pA [n=28], respectively). The inactivation kinetics of I(Ca-L) showed subtle differences with increased tau fast and tau slow decay constants in cardiomyocytes of SERCA2a transgenic animals. Beta-adrenergic stimulation with 50 nM isoproterenol reduced tau fast and tau slow decay constants in cardiomyocytes of transgenic rats to values that were not significantly different from those in normal cardiomyocytes. Furthermore, isoproterenol enhanced I(Ca-L) currents 3.2-fold and 2.3-fold in cardiomyocytes with and without the SERCA2a transgene, respectively, and this effect was abolished by buffering intracellular Ca(2+) with BAPTA. CONCLUSIONS: These findings indicate that enhanced Ca(2+) cycling in the hearts of SERCA2a transgenic rats, both under normal conditions and during beta-adrenergic stimulation, involves changes in I(Ca-L) currents. Modified I(Ca-L) kinetics may contribute, to some extent, to the improved contractile function of the myocardium of transgenic rats.

Time of admission, quality of PCI care, and outcome of patients with ST-elevation myocardial infarction.

OBJECTIVE: Our study aimed to analyse the hospital mortality of patients admitted in- and off-regular working hours with ST-elevation myocardial infarction (STEMI) within the special logistical setting of the urban area of the city of Berlin. BACKGROUND: There is a debate whether patients with acute myocardial infarction admitted to hospital outside regular working hours experience higher mortality rates than those admitted within regular working hours. METHODS: This study analyses data from the Berlin Myocardial Infarction Registry and comprises 2,131 patients with STEMI and treated with percutaneous coronary intervention (PCI) in 2004-2007. Data of patients admitted during in- and off-regular working hours were compared. RESULTS: There was significant difference in door-to-balloon time (median in-hours: 79 min; median off-hours: 90 min, p < 0.001) and in hospital mortality (in-hours: 4.3%; off-hours: 6.8%, p = 0.020) between STEMI patients admitted in- and off-hours for treatment with PCI. After adjustment, admission off-hours remained an independent predictor for in-hospital death for patients (OR = 2.50; 95% CI 1.38-4.56). In patients with primary care from physician-escorted Emergency Medical Services (EMS), door-to-balloon time was reduced by 10 min for in-hours as well as off-hours patients. The difference in hospital mortality between off-hour and in-hour admission was reduced to a non-significant OR = 1.61 (95% CI 0.79-3.27). CONCLUSIONS: In conclusion, patients admitted off-hours experienced longer door-to-balloon times and higher hospital mortality than did those admitted in-hours. The differences observed between patients admitted in-hours and off-hours were reduced through physician-escorted EMS reflecting the influence of optimized STEMI care.