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Objective Atrial fibrillation (AF) is the most common cardiac arrhythmia, and radiofrequency catheter ablation of AF (RCAAF) has become increasingly popular. Cardiac stress and inflammation have been associated with AF. This study was performed to determine whether the pre- or post-AF ablation levels of high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro–B-type natriuretic peptide (NT-proBNP) are predictive of AF recurrence. Methods This multicenter prospective cohort study involved patients undergoing RCAAF in Switzerland and Canada. The primary endpoint was the recurrence of AF or atrial flutter at 6 months. Results Of 202 patients, 195 completed follow-up (age, 57.5 ± 9 years; mean left ventricular ejection fraction, 62%; mean left atrial size, 19.4 cm2). Patients with AF recurrence had larger atrial surfaces and longer total RCAAF times. Both the pre-ablation hs-CRP level and 1-day post-RCAAF NT-proBNP level were significantly associated with an increased risk of recurrence. Conclusions The pre-ablation hs-CRP level and immediate post-ablation NT-proBNP level were markers for atrial arrhythmia recurrence after RCAAF. This confirms growing evidence of the role of inflammation in the pathogenesis of AF. These biomarkers appear to be promising stratification tools for selection and management of patients undergoing RCAAF.

Aims We aimed to identify a novel biomarker involved in the early events leading to an acute coronary syndrome (ACS) and evaluate its role in diagnosis and risk stratification. Methods and results Biomarker identification was based on gene expression profiling. In coronary thrombi of ACS patients, cysteine-rich angiogenic inducer 61 (Cyr61, CCN1) gene transcripts were highly up-regulated compared with peripheral mononuclear cells. In a murine ischaemia-reperfusion model (I/R), myocardial Cyr61 expression was markedly increased compared with the controls. Cyr61 levels were determined in human serum using an enzyme-linked immunosorbent assay. Cohorts of ACS (n = 2168) referred for coronary angiography, stable coronary artery disease (CAD) (n = 53), and hypertrophic obstructive cardiomyopathy (HOCM) patients (n = 15) served to identify and evaluate the diagnostic and prognostic performance of the biomarker. Cyr61 was markedly elevated in ST-elevation myocardial infarction patients compared with non-ST-elevation myocardial infarction/unstable angina or stable CAD patients, irrespective of whether coronary thrombi were present. Cyr61 was rapidly released after occlusion of a septal branch in HOCM patients undergoing transcoronary ablation of septal hypertrophy. Cyr61 improved risk stratification for all-cause mortality when added to the reference GRACE risk score at 30 days (C-statistic 0.88 to 0.89, P = 0.001) and 1 year (C-statistic 0.77 to 0.80, P

The aim of this study was to characterize iron deficiency (ID) in acutely decompensated heart failure (ADHF) and identify whether ID is associated with dyspnea class, length of stay (LOS), biomarker levels, and echocardiographic indices of diastolic function in patients with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). Consecutive patients admitted with ADHF at a single tertiary center were included. Demographic information, pathology investigations, and metrics regarding hospital stay and readmission were recorded. Patients were classified as having &lsquo, absolute&rsquo, ID if they had a ferritin level &lt, 100 ng/mL, or &lsquo, functional&rsquo, ID if they had a ferritin 100&ndash, 200 ng/mL and a transferrin saturation &lt, 20%. Of 503 patients that were recruited, 270 (55%) had HFpEF, 160 (33%) had HFREF, and 57 (12%) had heart failure with mid-range ejection fraction. ID was present in 54% of patients with HFrEF and 56% of patients with HFpEF. In the HFpEF group, ID was associated with a LOS of 11 &plusmn, 7.7 vs. 9 &plusmn, 6 days in iron replete patients, p = 0.036, and remained an independent predictor of increased LOS in a multivariate linear regression incorporating comorbidities, age, and ID status. This study corroborates a high prevalence of ID in both HFrEF and HFpEF, and further shows that in patients with HFpEF there is a prolongation of LOS not seen in HFrEF which may indicate a more prominent role for ID in HFpEF.

Introduction Current guidelines recommend angiography within 24 hours of hospitalisation for patients with non-ST elevation myocardial infarction (NSTEMI). The recent VERDICT study found that angiography within 12 hours of hospitalisation was associated with improved cardiovascular outcomes among high-risk patients. We aimed to obtain a real-world perspective of the impact of angiography timing on one-year outcomes of patients admitted with NSTEMI. Methods Data was obtained from the SPUM-ACS registry, a cohort of consecutive patients hospitalised with acute coronary syndromes in four university hospitals in Switzerland between 2009 and 2017. Patients without a door-to-catheter (DTC) time and those with life-threatening features were excluded. Cox proportional hazards models evaluated the impact of DTC time on the primary endpoint, defined as one-year major adverse cardiovascular events (MACE: cardiovascular mortality, myocardial infarction, stroke), and on one-year all-cause mortality. Results Of 2,672 NSTEMI patients, 1,832 met the inclusion criteria. Among them, 1,464 patients underwent angiography within 12 hours of admission (12h group) while 368 patients underwent angiography between 12 and 24 hours (12–24h group). After 2:1 propensity score matching, 736 patients from the 12h group and 368 patients from the 12–24h group were deemed equivalent in terms of main baseline clinical characteristics. Multiple logistic regression identified admission out-of-hours (night or weekend) as the most significant factor associated with delayed angiography. Cox models found no significant association between early angiography and one-year MACE (12h group: n=57 (7.7%) vs. 12–24h group: n=27 (7.3%), HR: 1.050, 95% CI 0.637- 1.733, p=0.847), or one-year all-cause mortality (12h group: n=25 (3.4%) vs. 12–24h group: n=17 (4.6%), HR: 1.514, 95% CI 0.774- 2.962, p=0.225) (Figure 1A). After stratification based on GRACE score (>140 vs. ≤140), there was no significant difference in one-year MACE or one-year all-cause mortality in the 12h group compared with the 12–24h group (p for interaction=0.601 and 0.463, respectively) (Figure 1A + 1B). Figure 1 Conclusion In an unselected real-world cohort of NSTEMI patients, angiography within 12 hours of hospitalisation was not associated with improved one-year outcomes when compared with angiography between 12 and 24 hours, even among patients with an elevated GRACE score.

The prognostic value of pulmonary hypertension (PH) estimated by echocardiography in unselected patients with acute decompensated heart failure (ADHF) is poorly studied. Between November 2014 and September 2018, 657 patients were recruited in a prospective registry of ADHF (ClinicalTrials.gov NCT02444416). The probability of pulmonary hypertension was based on European Society of Cardiology (ESC) guidelines for echocardiographic evaluation. The median survival without all-cause mortality or readmission was 7 months. During the median follow-up period of 15 months, there were 450 events including 185 deaths. In multivariate analysis, the hazard ratio (HR) of all-cause mortality or readmission for patients with a high probability of PH was 1.67 (95% CI 1.29&ndash, 2.17, p &lt, 0.001) as compared to patients with a low or intermediate probability. The left ventricular ejection fraction (LVEF) and right ventricular function (RVF) were not associated with the primary outcome&mdash, HR 1.02 (95% CI 0.81&ndash, 1.29, p = 0.84) and 0.96 (95% CI 0.76&ndash, 1.23, p = 0.77) respectively. In patients admitted for ADHF, a high probability of PH as evaluated by echocardiography provided the highest independent prognostic value for mortality and readmission, whereas LVEF and RVF were not associated with prognosis. The identification of patients at high risk of PH by non-invasive measurement conveys important prognostic information and may guide management.

BACKGROUND The relevance of the IMPROVE-IT trial on real-life practice has not been explored in patients with ACS. METHODS A prospective Swiss cohort of 6266 patients hospitalized for ACS between 2009 and 2017 with a one-year follow-up. The primary endpoints were the ezetimibe use overall or in combination with high-intensity statin at discharge and at one year after ACS. Secondary endpoint was LDL-C target achievement at one year in a subsample of 2984 patients. Relative Ratios (RR) were used to assess changes in primary endpoints before and after the publication of IMPROVE-IT, adjusting for age, sex, diabetes, prior myocardial infarction, LDL-C and attendance to cardiac rehabilitation. RESULTS The period following the publication of the IMPROVE-IT trial was associated with a steady increase in the use of ezetimibe at discharge (from 1.8% to 3.8%, P

The derivation and implementation of the natural switching surfaces (NSS) considering certain parametric uncertainties for a flyback converter operating in the boundary conduction mode is the main focus of this paper. The NSS with nominal parameters presents many benefits for the control of nonlinear systems; for example, fast transient response under load-changing conditions. However, the performance worsens considerably when the converter actual parameters are different from the ones used in the design process. Therefore, a novel control strategy for NSS considering the effects of parameter uncertainties is proposed. This control law can estimate and adapt the control trajectories in a minimum number of switching cycles to obtain excellent performances even under extreme parameter uncertainties. The analytical derivation of the proposed adaptive switching surfaces is presented together with simulations and experimental results showing adequate performance under different tests, including comparisons with a standard PI controller. Fil: Garcia Rodriguez, Luciano Andrés. University of Arkansas; Estados Unidos Fil: Chiacchiarini, Hector Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones en Ingeniería Eléctrica "Alfredo Desages". Universidad Nacional del Sur. Departamento de Ingeniería Eléctrica y de Computadoras. Instituto de Investigaciones en Ingeniería Eléctrica "Alfredo Desages"; Argentina. Universidad Nacional del Sur. Departamento de Ingeniería Eléctrica y de Computadoras; Argentina Fil: Carballo Rojas, David. University of Arkansas; Estados Unidos Fil: Balda, Juan Calros. University of Arkansas; Estados Unidos

Autoantibodies against apolipoprotein A-I (anti-apoA-I IgGs) are prevalent in atherosclerosis-related conditions. It remains elusive whether they improve the prognostic accuracy of the Global Registry of Acute Coronary Events (GRACE) score 2.0 (GS) in acute coronary syndromes (ACS). In this prospective multicenter registry, 1713 ACS patients were included and followed for 1 year. The primary endpoint (major adverse cardiovascular events (MACE)) was defined as the composite of myocardial infarction, stroke (including transient ischemic attack), or cardiovascular (CV) death with individual events independently adjudicated. Plasma levels of anti-apoA-I IgGs upon study inclusion were assessed using ELISA. The association between anti-apoA-I IgGs and incident MACE was assessed using Cox models with splines and C-statistics. One-year MACE incidence was 8.4% (144/1713). Anti-apoA-I IgG levels were associated with MACE with a non-linear relationship (p = 0.01), which remained unchanged after adjusting for the GS (p = 0.04). The hazard increased progressively across the two first anti-apoA-I IgG quartiles before decreasing thereafter. Anti-apoA-I IgGs marginally improved the prognostic accuracy of the GS (c-statistics increased from 0.68 to 0.70). In this multicenter study, anti-apoA-I IgGs were predictive of incident MACE in ACS independently of the GS but in a nonlinear manner. The practical implications of these findings remain to be defined.

The main objective of this research work is to develop a new low-cost isolated three-level ac-dc power converter topology that is suitable for applications having high input ac voltages and high output currents; for example, hybrid (ac-dc) microgrids or offshore wind farms. Existing three-level converter topologies convert ac power to dc power while maintaining requirements set by international standards for power conversion. These types of converters have significant conduction losses due to high currents in the low-voltage side and high costs, particularly when using several devices in series or in parallel to achieve high-voltage and high-power levels. The proposed topology replaces the conventional three-level converters in the low-voltage side by only two controlled devices and four diodes while still maintaining the basic functionality of a three-level converter. Simulation results for a 87.5-kW case study and experimental results on a 250-W scale-down prototype demonstrate the feasibility of the proposed ideas.

BACKGROUND Minimal lipoprotein(a) [Lp(a)] target values are advocated for high-risk cardiovascular patients. We investigated the prognostic value of Lp(a) in the acute setting of patients with acute coronary syndromes (ACS). METHODS Plasma levels of Lp(a) were collected at time of angiography from 1711 patients hospitalized for ACS in a multicenter Swiss prospective cohort. Associations between elevated Lp(a) ≥ 30 mg/dL (cut-off corresponding to the 75 percentile of the assay) or Lp(a) tertiles at baseline, and major adverse cardiovascular events (MACE) at 1-year, defined as a composite of cardiac death, myocardial infarction or stroke were assessed using hazard ratios (HR) and 95% confidence intervals (CI) adjusting for traditional cardiovascular risk factors (age, sex, smoking, diabetes, hypertension, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C] and triglycerides. RESULTS Lp(a) levels range between 2.5 mg/dL to 132 mg/dL with a median value of 6 mg/dL and a mean value of 14.2 mg/dL. A total of 276 patients (23.0%) had Lp(a) plasma levels ≥ 30 mg/dL). Patients with elevated Lp(a) were more likely to be of female gender, and to have higher levels of total cholesterol, LDL-C, HDL-C and triglycerides. Higher Lp(a) was associated with failure to reach the LDL-C target < 1.8 mmol/l at 1-year (HR 1.71, 95% CI 1.13-2.58, P=0.01). No association was found between elevated Lp(a) and MACE at 1 year (HR 1.05, 95% CI 0.64-1.73), nor for Lp(a) tertiles (HR 0.82, 95% CI 0.52-1.28, P >0.20) or standardized continuous variables (0.98, 95% CI 0.82-1.19 for each increase of standard deviation). CONCLUSIONS Our real-world data suggest high Lp(a) levels at time of angiography are not predictive for cardiovascular outcomes in patients otherwise medically well controlled, but might be useful to identify patients who would not be on LDL-C targets one year after ACS. This article is protected by copyright. All rights reserved.

Background The gradual implementation of evidence-based treatment strategies has improved outcomes in patients with acute coronary syndromes (ACS). The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) was published on June 3rd, 2015, but its relevance on real life practice has not been explored. Methods We analyzed a prospective Swiss cohort of 6266 patients hospitalized for ACS between 2009 and 2017. The primary endpoints were the ezetimibe use overall or in combination with high-intensity statin at discharge and at one year after ACS. Secondary endpoint was LDL-C target achievement at one year in a subsample of 2984 patients. Relative Ratios (RR) were used to assess changes in primary endpoints before and after the publication of IMPROVE-IT, adjusting for age, sex, pre-existing diabetes, history of myocardial infarction, baseline low-density lipoprotein cholesterol (LDL-C) and attendance to cardiac rehabilitation. Results The period following the publication of the IMPROVE-IT trial was associated with an overall increase in the use of ezetimibe at discharge (from 1.8% to 3.8%, P Conclusion After the publication of the IMPROVE-IT trial, the use of ezetimibe was increased by three-fold in a large contemporary cohort of ACS patients, concomitant with an improved LDL-C target achievement.

BackgroundStructured secondary cardiovascular prevention programs (SSCP) following acute coronary syndromes (ACS) may reduce major adverse cardiovascular events (MACE) through better adherence to post-ACS recommendations.MethodsThrough a prospective multicenter cohort study, we compared the outcomes of two sequential post-ACS patient cohorts, the initial one receiving standard care (SC) followed by one receiving additional interventions (SSCP) aimed at improving patient education as well as healthcare provider and hospital systems. The primary endpoint was MACE at one year. Secondary endpoints included adherence to recommended therapies, attendance to cardiac rehabilitation (CR) and successful achievement of cardiovascular risk factor (CVRF) targets.ResultsIn total, 2498 post-ACS patients from 4 Swiss university hospitals were included: 1210 vs 1288 in the SC and SSCP groups, respectively. The SSCP group demonstrated a significant increase in attendance to CR programs (RR 1.08, 95%CI 1.02-1.14, P = 0.006), despite not achieving the primary MACE endpoint (HR 0.97, 95%CI 0.77-1.22, P = 0.79). After age-stratification, significant reductions in cardiac death, MI and stroke events (HR 0.53, 95%CI 0.30-0.93, P for interaction = 0.016) were observed for SSCP patients ≤ 65 years old. The SSCP group also scored significantly better for the LDL cholesterol target (RR 1.07, 95%CI 1.02-1.13, P = 0.012), systolic blood pressure target (RR 1.06, 95%CI 1.01-1.13, P = 0.029) and physical activity (RR 1.10, 95%CI 1.01-1.20, P = 0.021).ConclusionsThe implementation of an SSCP post ACS was associated with an improvement in the control of CVRF and attendance to CR programs, and was also associated with significant reductions in cardiac death, MI and stroke at one year for patients ≤65years old.

Over recent decades, research into the causes and mechanisms driving the development of cardiovascular disease has rapidly evolved. In everyday real life, this translates into ever more targeted treatment strategies that can be adapted to each individual’s cardiovascular history and risk.

BACKGROUND: Patients with heterozygous familial hypercholesterolemia (FH) and coronary heart disease have high mortality rates. However, in an era of high-dose statin prescription after acute coronary syndrome (ACS), the risk of recurrent coronary and cardiovascular events associated with FH might be mitigated. We compared coronary event rates between patients with and without FH after ACS. METHODS: We studied 4534 patients with ACS enrolled in a multicenter, prospective cohort study in Switzerland between 2009 and 2013 who were individually screened for FH on the basis of clinical criteria according to 3 definitions: the American Heart Association definition, the Simon Broome definition, and the Dutch Lipid Clinic definition. We used Cox proportional models to assess the 1-year risk of first recurrent coronary events defined as coronary death or myocardial infarction and adjusted for age, sex, body mass index, smoking, hypertension, diabetes mellitus, existing cardiovascular disease, high-dose statin at discharge, attendance at cardiac rehabilitation, and the GRACE (Global Registry of Acute Coronary Events) risk score for severity of ACS. RESULTS: At the 1-year follow-up, 153 patients (3.4%) had died, including 104 (2.3%) of fatal myocardial infarction. A further 113 patients (2.5%) experienced nonfatal myocardial infarction. The prevalence of FH was 2.5% with the American Heart Association definition, 5.5% with the Simon Broome definition, and 1.6% with the Dutch Lipid Clinic definition. Compared with patients without FH, the risk of coronary event recurrence after ACS was similar in patients with FH in unadjusted analyses, although patients with FH were >10 years younger. However, after multivariable adjustment including age, the risk was greater in patients with FH than without, with an adjusted hazard ratio of 2.46 (95% confidence interval, 1.07–5.65; P =0.034) for the American Heart Association definition, 2.73 (95% confidence interval, 1.46–5.11; P =0.002) for the Simon Broome definition, and 3.53 (95% confidence interval, 1.26–9.94; P =0.017) for the Dutch Lipid Clinic definition. Depending on which clinical definition of FH was used, between 94.5% and 99.1% of patients with FH were discharged on statins and between 74.0% and 82.3% on high-dose statins. CONCLUSIONS: Patients with FH and ACS have a >2-fold adjusted risk of coronary event recurrence within the first year after discharge than patients without FH despite the widespread use of high-intensity statins.

Au debut de l’annee 2018, le Groupe de travail Suisse Lipides et Atherosclerose (GSLA) a actualise ses recommandations pour la prevention de l’atherosclerose et publie une nouvelle version du guide de poche GSLA du meme nom.

Die Schweizer Arbeitsgruppe Lipide und Atherosklerose (AGLA) hat Anfang 2018 ihre Empfehlungen zur Pravention der Atherosklerose aktualisiert und eine neue Version des gleichnamigen AGLA-Pocketguides herausgegeben.

Microgrid are gaining popularity due to several advantages like potential for fuel savings and resiliency in case of grid catastrophic failures. In a microgrid, many energy sources like wind and solar farms are connected to the grid through inverters with different power ratings and LCL filter parameters. The inverters incorporated in these systems might have a different frequency response and stability ranges than those inverters with identical LCL filter values. This paper establishes the model and analyzes the stability of a system with multiple paralleled-and grid-connected inverters with different LCL filter paramenters using the grid-side currents as feedback signals. The analysis results showed that a method similar to the interactive and common current analysis technique used on inverters with identical LCL filters can be implemented on a system with different LCL filers to calculate the maximum values of the inverters' current controller gains without having to derive the complicated equations of the MIMO system.

BACKGROUND AND AIMS Pulse pressure (PP) is a surrogate of aortic stiffness (AS) easily obtainable. The link between AS and cardio-vascular disease is documented, however, data regarding acute coronary syndrome (ACS) patients are scarce and contradictory. We aimed to assess the prognostic value of PP measured at admission, with regard to major adverse outcomes (all-cause mortality, recurrence of MI, and stroke), during the first year following an acute coronary syndrome (ACS). METHODS The SPUM-ACS project is a prospective cohort study of patients with ACS conducted in 4 Swiss University hospitals. Patients with no PP at admission or with severe clinical heart failure or cardiogenic shock were excluded. Cox regression analyses were performed to determine associations between PP and outcomes (all-cause mortality, recurrence of myocardial infarction (MI), and stroke). Three multivariate Cox regression models were adjusted for hemodynamic, cardiovascular, and non-cardiovascular confounders, added successively. RESULTS Of 5635 eligible patients, 5070 met the inclusion criteria. Mean patient age was 63 years (range: 54-72), 79.6% were male, and mean blood pressure and PP were 93.9 ± 15.6 and 54 ± 17 mmHg, respectively. Multivariate analyses confirmed the prognostic significance of PP for each 10-mmHg increase for the composite endpoint, hazard ratio (HR) 1.126 [1.051-1.206], p = 0.001; all-cause mortality, HR1.129 [1.013-1.260], p = 0.029; and recurrence of MI, HR1.206 [1.102-1.320], p

Background: Randomised controlled trials have provided conflicting results regarding procedural and clinical outcomes of thrombus aspiration combined with percutaneous coronary intervention, when compared with primary percutaneous coronary intervention alone in patients with acute coronary syndromes. Methods: Acute coronary syndrome patients referred for coronary angiography to four Swiss university hospitals between 2009 and 2012 were enrolled in the SPUM–ACS cohort. At the discretion of the interventional cardiologist, patients underwent thrombus aspiration with percutaneous coronary intervention or percutaneous coronary intervention alone. Procedural success was defined as post-procedural thrombolysis in myocardial infarction III flow in the infarct-related artery. Serial changes in high-sensitivity troponin T (ΔhsTnT) and adjudicated 30 days (1 year) clinical events defined as the composite of cardiac death, recurrent myocardial infarction or clinically indicated coronary revascularisation were assessed. Results: Among 1641 patients, 777 (47.4%) had angiographic evidence of coronary thrombus. Patients were categorised into thrombus aspiration with percutaneous coronary intervention ( n=663) or percutaneous coronary intervention alone ( n=114). ST-segment elevation myocardial infarction (STEMI) patients more often received thrombus aspiration with percutaneous coronary intervention (87.8%) than non-STEMI patients (73.5%), PConclusions: In this real-world acute coronary syndrome cohort, patients treated by thrombus aspiration with percutaneous coronary intervention showed no difference in the restoration of coronary blood flow compared with percutaneous coronary intervention alone immediately after the procedure. Furthermore, ΔhsTnT and clinical outcomes at either 30 days or 1 year were similar between thrombus aspiration with percutaneous coronary intervention or percutaneous coronary intervention alone. Clinical Trials Registration: SPUM–ACS cohort NCT01000701

Background Many parameters can affect the level of inflammation during acute coronary syndromes (ACS). We aimed to assess the one-year risk of major adverse cardiovascular events (MACE) and bleeding associated with elevated hsCRP levels during ACS, taking into account the severity of myocardial infarction, the timing of blood sampling and established long-term prognostic factors. Methods We studied 1864 consecutive patients with ACS enrolled in a contemporary multicenter prospective cohort study in Switzerland. HsCRP levels were determined at hospital admission. One year after discharge MACE and bleeding events were assessed. Multivariable adjusted Cox proportional hazards were computed with age, sex, time from symptom onset to blood draw, body mass index, current smoking, hypertension, diabetes mellitus, pre-existing cardiovascular disease, history of inflammatory disease, LDL-cholesterol levels, type of ACS, left ventricular ejection fraction and GRACE 1.0 risk score. Results At one-year follow-up, 151 (8.1%) patients suffered MACE. Compared to patients with hsCRP below 2 mg/l, the risk of MACE was higher in patients with hsCRP levels between 2 and 5 mg/l, with a multivariate adjusted hazard ratio (HR) of 1.63 (95% confidence interval (CI) 0.93–2.84), in those with levels between 5 and 10 mg/l, with a HR of 2.80 (95% CI 1.58–4.96), and in those with levels above 10 mg/l, with a HR of 2.23 (95% CI 1.28–3.88). There was no difference in bleeding risk between the four groups. Conclusions Systemic inflammation in the acute phase of myocardial infarction is an independent predictor for cardiovascular events, but not for bleeding.

Distributed generation is gaining greater penetration levels in distribution grids due to government incentives for integrating distributed energy resources (DERs) and DER cost reductions. The frequency response of a grid-connected single inverter changes as other inverters are connected in parallel due to the couplings among grid inductance and/or inverter output filters. The selection of the inverter- or grid-side currents as feedback control signals is then not trivial because each one has tradeoffs. This paper analyses the system stability for multiple parallel- and grid-connected inverters using the inverter- or grid-side currents as feedback signals. Modeling of both feedback signals is performed using the current separation technique. Morover, the stability range for different conditions including active damping is analyzed through the root locus technique. The grid-side current has a wider range of stability, but the inverter-side current allows for higher values of the proportional gain near the critical frequency and no extra sensors are needed since measurement of the inverter current is needed for protection in high-power applications.

Atrial fibrillation (AF) appears in the presence or absence of structural heart disease. The majority of foci causing AF are located near the ostia of pulmonary veins (PVs), where cardiomyocytes and vascular smooth muscle cells interdigitate. Connexins (Cx) form gap junction channels and participate in action potential propagation. Genetic variants in genes encoding Cx40 and Cx37 affect their expression or function and may contribute to PV arrhythmogenicity. DNA was obtained from 196 patients with drug-resistant, symptomatic AF with and without structural heart disease, who were referred for percutaneous catheter ablation. Eighty-nine controls were matched for age, gender, hypertension, and BMI. Genotyping of the Cx40 −44G > A, Cx40 +71A > G, Cx40 −26A > G, and Cx37 1019C > T polymorphisms was performed. The promoter A Cx40 polymorphisms (−44G > A and +71A > G) showed no association with non-structural or structural AF. Distribution of the Cx40 promoter B polymorphism (−26A > G) was different in structural AF when compared to controls (p = 0.03). There was no significant difference with non-structural AF (p = 0.50). The distribution of the Cx37 1019C > T polymorphism was different in non-structural AF (p = 0.03) but not in structural AF (p = 0.08) when compared to controls. Our study describes for the first time an association of drug-resistant non-structural heart disease AF with the Cx37 1019C > T gene polymorphism. We also confirmed the association of the Cx40 − 26G > A polymorphism in patients with AF and structural disease.

Objectives The aim of this study was to assess the safety of the concurrent administration of a clopidogrel and prasugrel loading dose in patients undergoing primary percutaneous coronary intervention. Background Prasugrel is one of the preferred P2Y12 platelet receptor antagonists for ST-segment elevation myocardial infarction patients. The use of prasugrel was evaluated clinically in clopidogrel-naive patients. Methods Between September 2009 and October 2012, a total of 2,023 STEMI patients were enrolled in the COMFORTABLE (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI]) and the SPUM-ACS (Inflammation and Acute Coronary Syndromes) studies. Patients receiving a prasugrel loading dose were divided into 2 groups: 1) clopidogrel and a subsequent prasugrel loading dose; and 2) a prasugrel loading dose. The primary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding in hospital at 30 days. Results Of 2,023 patients undergoing primary percutaneous coronary intervention, 427 (21.1%) received clopidogrel and a subsequent prasugrel loading dose, 447 (22.1%) received a prasugrel loading dose alone, and the remaining received clopidogrel only. At 30 days, the primary safety endpoint was observed in 1.9% of those receiving clopidogrel and a subsequent prasugrel loading dose and 3.4% of those receiving a prasugrel loading dose alone (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.25 to 1.30, p = 0.18). The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) bleeding score tended to be higher in prasugrel-treated patients (p = 0.076). The primary safety endpoint results, however, remained unchanged after adjustment for these differences (clopidogrel and a subsequent prasugrel loading dose vs. prasugrel only; HR: 0.54 [95% CI: 0.23 to 1.27], p = 0.16). No differences in the composite of cardiac death, myocardial infarction, or stroke were observed at 30 days (adjusted HR: 0.66, 95% CI: 0.27 to 1.62, p = 0.36). Conclusions This observational, nonrandomized study of ST-segment elevation myocardial infarction patients suggests that the administration of a loading dose of prasugrel in patients pre-treated with a loading dose of clopidogrel is not associated with an excess of major bleeding events. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI] [COMFORTABLE]; NCT00962416; and Inflammation and Acute Coronary Syndromes [SPUM-ACS]; NCT01000701).

2013 AHA/ACC guidelines on the treatment of cholesterol advised to tailor high-intensity statin after ACS, while previous ATP-III recommended titration of statin to reach low-density lipoprotein cholesterol (LDL-C) targets. We simulated the impact of this change of paradigm on the achievement of recommended targets.Among a prospective cohort study of consecutive patients hospitalized for ACS from 2009 to 2012 at four Swiss university hospitals, we analyzed 1602 patients who survived one year after recruitment. Targets based on the previous guidelines approach was defined as (1) achievement of LDL-C target 1.8 mmol/l, (2) reduction of LDL-C ≥ 50% or (3) intensification of statin in patients who did not reach LDL-C targets. Targets based on the 2013 AHA/ACC guidelines approach was defined as the maximization of statin therapy at high-intensity in patients aged ≤75 years and moderate- or high-intensity statin in patients75 years.1578 (99%) patients were prescribed statin at discharge, with 1120 (70%) at high-intensity. 1507 patients (94%) reported taking statin at one year, with 909 (57%) at high-intensity. Among 482 patients discharged with sub-maximal statin, intensification of statin was only observed in 109 patients (23%). 773 (47%) patients reached the previous LDL-C targets, while 1014 (63%) reached the 2013 AHA/ACC guidelines targetsone year after ACS (p value 0.001).The application of the new 2013 AHA/ACC guidelines criteria would substantially increase the proportion of patients achieving recommended lipid targets one year after ACS. Clinical trial number, NCT01075868.

OBJECTIVE To assess safety up to 1 year of follow up associated with prasugrel and clopidogrel use in a prospective cohort of patients with acute coronary syndromes (ACS). METHODS Between 2009 and 2012 2286 patients invasively managed for ACS were enrolled in the multicentre Swiss ACS Bleeding Cohort among whom 2148 patients received either prasugrel or clopidogrel according to current guidelines. Patients with ST elevation myocardial infarction (STEMI) preferentially received prasugrel while those with non STEMI a history of stroke or transient ischaemic attack age =75 years or weight

Background The American College of Cardiology (ACC) and European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) have recently published recommendations for the use of proprotein convertase subtilisin/kexin‐9 ( PCSK 9) inhibitors in situations of very high risk. We aim to assess in the real world the suitability of PCSK 9 inhibitors for acute coronary syndromes. Methods and Results We analyzed a prospective Swiss cohort of 2023 patients hospitalized for acute coronary syndromes between 2009 and 2014 with available data for low‐density lipoprotein cholesterol and lipid‐lowering therapy at 1 year. Clinical familial hypercholesterolemia was defined using the Dutch Lipid Clinic Network algorithm as unlikely, possible, probable, or definite. We simulated a fixed relative reduction of 24% in low‐density lipoprotein cholesterol levels at 1 year in all patients not treated with ezetimibe, irrespective of the low‐density lipoprotein cholesterol levels and statin regimen. At 1 year, 94.3% of patients were treated with statin, 5.8% with ezetimibe, and 35.8% of patients had on‐target low‐density lipoprotein cholesterol levels (PCSK 9 inhibitors at 1 year was 13.4% using American College of Cardiology criteria and 2.7% using European Society of Cardiology/European Atherosclerosis Society criteria. Patients with possible or probable/definite familial hypercholesterolemia were more eligible for PCSK 9 inhibitors compared with their non–familial hypercholesterolemia counterparts: 27.6% versus 8.8% according to American College of Cardiology criteria and 6.6% versus 1.8% according to European Society of Cardiology/European Atherosclerosis Society criteria ( P Conclusions Recommendations made by the American College of Cardiology guidelines would lead to 5‐fold higher eligibility rates for PCSK 9 inhibitors compared to the European Society of Cardiology/European Atherosclerosis Society consensus statement in acute coronary syndrome patients.

Various properties of digoxin have been exploited for decades, amongst which are its positive inotropy used in the treatment of heart failure, and its vagotonic effect used to slow ventricular response to atrial fibrillation. Pharmacologic properties of digoxin are however characterised by a narrow therapeutic interval, and recent observational studies suggest a potential association with increased mortality in patients with atrial fibrillation. As a result and because of available alternative therapeutic strategies, current guidelines do not recommend digoxin as first line treatment of atrial fibrillation. Digoxin may be considered in patients with heart failure and atrial fibrillation with rapid ventricular response when other therapeutic options cannot be pursued.Depuis de nombreuses années, la digoxine est utilisée dans le traitement de l’insuffisance cardiaque en raison de son inotropisme positif, et pour contrôler la réponse ventriculaire en présence de fibrillation auriculaire (FA) via ses propriétés vagotoniques. Caractérisée par une marge thérapeutique étroite, des études observationnelles récentes suggèrent que la digoxine pourrait être associée à une surmortalité chez les patients avec FA. Pour ces raisons, et du fait de nombreuses alternatives thérapeutiques, la digoxine n’est actuellement plus recommandée en première intention lors de FA. Elle peut être envisagée chez les patients présentant une insuffisance cardiaque et une FA à réponse ventriculaire rapide lorsque des traitements alternatifs ne peuvent être poursuivis.

Hybrid PET/MRI allows the acquisition of both fluorine-18-fluorodeoxyglucose (F-FDG) PET and cardiac magnetic resonance (CMR) during one session. Whether this will result in different referral to coronary revascularization (CR) is unknown. We compared this new hybrid method with all-nuclear/all-CMR methods in the assessment of viable myocardium and in downstream referral to CR.Overall, 12 patients with rest perfusion defects on a single photon emission computed tomography (SPECT) were recruited for cardiac viability assessment using a PET/MRI device. Perfusion (SPECT and CMR), metabolism, late gadolinium enhancement (LGE), and contractility were compared using a 20-segments bull's eye for agreement. The patterns of ischemia/viability were compared between all-nuclear, all-CMR, and hybrid methods. Downstream CR was proposed after correlating findings to coronary angiography.The SPECT and CMR perfusion denoted poor agreement [agreement rate (AR): 60%; κ: 0.191, P0.004]. The added PET metabolism concurred in reclassifying 19.2% of segments with intermediate or unassessable LGE using the hybrid method. Overall, the all-CMR method showed better agreement with the hybrid method than the all-nuclear method for findings of normal (AR: 100%, κ: 1.00 vs. 65.8% %; κ: 0.347, respectively; P0.001), scar (AR: 85%; κ: 0.675 vs. 80.8%; κ: 0.596, respectively; P0.001), and ischemic segments (AR: 95.8%; κ: 0.881 vs. 75.8%; κ: 0.168, respectively; P0.001). Downstream CR was proposed in four, 11, and 12 vessels by the all-nuclear, all-CMR, or hybrid methods, respectively.Compared with all-CMR, the hybrid method allowed the reclassification of 19.2% segments. Using CMR perfusion instead of SPECT perfusion had a significant impact on downstream target vessel revascularization.

Background Nighttime traffic noise is associated with sleep disturbances, but sleep fragmentation and sleep-disordered breathing (SDB) have not been demonstrated in individuals living near busy roads. Methods We asked 1383 participants to answer a health questionnaire and to undergo 24-h electrocardiogram (ECG). Nocturnal ECG records were used to calculate the very low frequency index (VLFI) interval, a surrogate marker of sleep fragmentation. Distances of participants' addresses to roadways were calculated using the VECTOR25© Swisstopo roads classification, a traffic noise proxy. Distances of homes within 100 or 50m of major roads defined proximity to busy roads. Adjusted multivariate logistic regressions analyzed associations between the distance of home to main roads and VLFI or self-reported SDB. Results Distance of participants' homes to main roads was significantly associated with the VLFI in women (odds ratio [OR], 1.58 [confidence interval {CI}, 1.03–2.42]; P =.038) but not in men (OR, 1.35 [CI, 0.77–2.35]; P =.295). Women under hormonal replacement therapy (HRT) were at higher risk for increased VLFI when living close to main roads (OR, 2.10 [CI, 1.20–3.68]; P =.01) than untreated women ( P =.584). Associations with self-reported SDB were not statistically relevant. Conclusions In our large population, women living close to main roads were at significantly higher risk for sleep fragmentation than men. The 2-fold higher risk for menopausal women under HRT underscores the vulnerability of this group.

Accurate markers of atrial fibrillation (AF) recurrences after electrical cardioversion (ECV) are lacking. This study was conducted to assess the value of P-wave signal averaging (SAPW) for predicting AF recurrences in a nonselected patients population submitted to ECV.

As discussed previously in this book, a biomarker is “a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention” [3]. Cardiovascular biomarkers are usually classified in three main categories according to their potential use

Introduction Length of hospital stay (LHS) is an indicator of clinical effectiveness. Early hospital discharge (≤72 hours) is recommended in patients with acute coronary syndromes (ACS) at low risk of complications, but reasons for prolonged LHS poorly reported. Methods We collected data of ACS patients hospitalized at the Geneva University Hospitals from 1st July 2013 to 30th June 2015 and used the Zwolle index score to identify patients at low risk (≤ 3 points). We assessed the proportion of eligible patients who were successfully discharged within 72 hours and the reasons for prolonged LHS. Outcomes were defined as adherence to recommended therapies, major adverse events at 30 days and patients' satisfaction using a Likert-scale patient-reported questionnaire. Results Among 370 patients with ACS, 255 (68.9%) were at low-risk of complications but only 128 (50.2%)were eligible for early discharge, because of other clinical reasons for prolonged LHS (e.g. staged coronary revascularization, cardiac monitoring) in 127 patients (49.8%). Of the latter, only 45 (35.2%) benefitted from an early discharge. Reasons for delay in discharge in the remaining 83 patients (51.2%) were mainly due to delays in additional investigations, titration of medical therapy, admission or discharge during weekends. In the early discharge group, at 30 days, only one patient (2.2%) had an adverse event (minor bleeding), 97% of patients were satisfied by the medical care. Conclusion Early discharge was successfully achieved in one third of eligible ACS patients at low risk of complications and appeared sufficiently safe while being overall appreciated by the patients.

Background: Alterations in heart rate variability (HRV) are a potential link between exposure to traffic-related air pollution and cardiovascular mortality. Objectives: We investigated whether long-term exposure to traffic-related PM10 (TPM10) is associated with HRV in older subjects and/or in participants taking specific cardiovascular treatment or with self-reported heart disease. Methods: We included 1607 subjects from the general population aged 50 to 72 years. These participants from the SAPALDIA cohort underwent ambulatory 24-hr electrocardiogram monitoring. Associations of average annual exposure to TPM10 over 10 years with HRV parameters from time and frequency domains were estimated using multivariable mixed linear models. Effect estimates are expressed as percent changes in geometric means. Results: HRV was only associated with TPM10 in participants under ACE inhibitor therapy (N=94). A 1 μg/m3 increment, approximately equivalent to an interquartile range, in 10 year average TPM10 was associated with decrements of 14.5% (95% confidence interval (CI), −25.9 to −1.3) in high frequency (HF) power, of 4.5% (−8.2 to −0.5) in the standard deviation of all normal-to-normal RR intervals (SDNN), of 10.6% (−18.5 to −1.9) in total power (TP) and an increase of 9.2% (0.8 to 20.2) in the LF/HF power ratio. Conclusions: In the absence of an overall effect our results suggest that alterations in HRV, a measure of autonomic control of the cardiac rhythm, may not be a central mechanism by which long-term exposure to TPM10 increases cardiovascular mortality. Novel evidence on an effect in persons under ACE inhibitor treatment needs to be confirmed in future studies. Keywords: HRV, Traffic-related PM10, Cardiovascular medication, ACE inhibitors, SAPALDIA

Background: Household cleaning products are associated with adverse respiratory health outcomes, but the cardiovascular health effects are largely unknown. Objective: We determined if long-term use of household sprays and scented products at home was associated with reduced heart rate variability (HRV), a marker of autonomic cardiac dysfunction. Methods: We recorded 24-hr electrocardiograms in a cross-sectional survey of 581 Swiss adults, ≥ 50 years of age, who answered a detailed questionnaire regarding their use of household cleaning products in their homes. The adjusted average percent changes in standard deviation of all normal-to-normal intervals in 24 hr (24-hr SDNN) and total power (TP) were estimated in multiple linear regression in association with frequency [< 1, 1–3, or 4–7 days/week, unexposed (reference)] of using cleaning sprays, air freshening sprays, and scented products. Results: Decreases in 24-hr SDNN and TP were observed with frequent use of all product types, but the strongest reductions were associated with air freshening sprays. Compared with unexposed participants, we found that using air freshening sprays 4–7 days/week was associated with 11% [95% confidence interval (CI): –20%, –2%] and 29% (95% CI: –46%, –8%) decreases in 24-hr SDNN and TP, respectively. Inverse associations of 24-SDNN and TP with increased use of cleaning sprays, air freshening sprays, and scented products were observed mainly in participants with obstructive lung disease (p < 0.05 for interactions). Conclusions: In predominantly older adult women, long-term frequent use of household spray and scented products was associated with reduced HRV, which suggests an increased risk of cardiovascular health hazards. People with preexisting pulmonary conditions may be more susceptible.

Background— Premature atrial contractions (PACs) are independent predictors of atrial fibrillation, stroke, and death. However, little is known about PAC frequency in the general population and its association with other cardiovascular risk factors. Methods and Results— We performed a cross-sectional analysis among participants of the population-based Swiss cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA). 24-hour Holter electrocardiograms to assess PAC prevalence and frequency were performed in a random sample of 1742 participants aged ≥50 years. The median (interquartile range) number of PACs per hour was 0.8 (0.4–1.8), 1.1 (0.5–2.4), 1.4 (0.7–4.6), 2.3 (0.8–6.9), and 2.6 (1.2–6.5) among participants aged 50 to 55, 55 to 60, 60 to 65, 65 to 70, and ≥70 years, respectively ( P P P P P P =0.002), and high-density lipoprotein cholesterol (RR per SD 0.80; P =0.0002). Hypertension and body mass index were not significantly related to PAC frequency. Conclusions— To our knowledge, this is the first study to assess risk factors for PAC frequency in the general population aged ≥50 years. PACs are common, and their frequency is independently associated with age, height, history of cardiovascular disease, natriuretic peptide levels, physical activity, and high-density lipoprotein cholesterol. The underlying mechanisms of these relationships need to be addressed in future studies.

Despite a marked improvement of in-hospital outcome of patients with Acute Coronary Syndrome (ACS), long-term outcome remains poor. There remains a high risk of complications, Non ST-Elevation ACS (NSTE-ACS) patients being at higher risk than those with ST-elevation ACS, in part due to more diffuse coronary artery disease. Whether with conservative medical management or an early invasive approach, of which they less frequently benefit, NSTE-ACS patients are less frequently treated according to guidelines. Therapeutic adhesion within the months following hospital discharge is low and associated with an increase in one-year mortality. The next step in the improvement of care of ACS patients will be to use multi-dimensional prevention programs that use didactic information tools and improve patient motivation, aimed at reinforcing the use of guidelines, promoting in-hospital therapeutic education, creating patient-health care provider partnerships and including discharge programs that ensure the prescription of recommended therapies.

OBJECTIVE To examine the prognosis of patients with cardiovascular and non-cardiovascular multimorbidity after acute coronary syndrome compared to patients without prior multimorbidity. METHODS This multicenter prospective cohort study in Switzerland included 5,635 patients hospitalized with acute coronary syndrome between 2009 and 2014, with a one-year follow-up period. We defined cardiovascular and non-cardiovascular multimorbidity as having at least two prior comorbidities before the index hospitalization. Multivariable adjusted Cox proportional models were built to assess the one-year risk of recurrent cardiovascular events, defined as cardiovascular mortality and non-fatal myocardial infarction or stroke. The final model was adjusted for age, gender, body mass index, tobacco consumption, education, and family history of cardiovascular disease, prescription of high-dose statinsat discharge and use of cardiac rehabilitation after discharge. RESULTS Overall, 3,664 patients (65%) had no multimorbidity, 1,839 (33%) had cardiovascular multimorbidity, 62 (1%) had non-cardiovascular multimorbidity, and 70 (1%) had both cardiovascular and non-cardiovascular multimorbidity. The multivariate risk of recurrent cardiovascular events was increased among patients with cardiovascular multimorbidity (hazard ratio (HR) 2.05, 95% CI: 1.54-2.73, p

Although cardiac MRI (CMR) provides accurate quantitative assessment of myocardial function, structure, and tissue characterization, there is growing evidence of the prognostic significance of CMR in the clinical setting. This article aims to not only review the diagnostic utility of CMR but all the prognostic implications in different cardiac conditions. First, CMR can distinguish ischemic from nonischemic cardiomyopathies and is establishing an increasing role in risk stratifying patients with heart failure. Second, CMR perfusion with vasodilator and inotropic stress has high sensitivity and specificity for prediction of cardiovascular events. Third, in addition to being an accurate tool for assessing myocardial viability and predicting the benefits of coronary revascularization, scar characterization by CMR late gadolinium enhancement imaging provides prognostic information beyond traditional markers of left ventricular function and volume. This article aims to explore the current evidence of each of these clinical settings.

Aims: To analyze the diagnostic yield of 24-h electrocardiographic monitoring (Holter) as a function of cardiac disease and electrocardiography (ECG) status in patients with unexplained syncope. Methods: Patients were considered as having unexplained syncope when a careful clinical history, physical and neurological examination, 12-lead ECG and testing for orthostatic hypotension were negative. All patients underwent 24-h Holter. According to the type of arrhythmias that occurred during monitoring, Holter was classified as: (1) normal, in the absence of significant arrhythmias; (2) abnormal, in the presence of significant (e.g. atrial fibrillation) but non-diagnostic arrhythmias; or (3) diagnostic, in the presence of serious arrhythmia (e.g. complete AV block) with simultaneous symptoms. Clinical features, ECG and echocardiography were used to stratify patients and identify those in whom electrophysiological studies (EPS) were indicated. Results: 140 consecutive patients with unexplained syncope underwent 24-h Holter and 44 of them (31%) had non-diagnostic arrhythmias. These occurred more frequently in patients with a positive cardiac history or an abnormal ECG (31/73, 42%), compared to patients without these features (13/67, 19%, p

We sought to determine the prevalence of orthostatic hypotension as a cause of syncope in the emergency setting, and describe the characteristics of patients diagnosed with this condition. Blood pressure orthostatic changes were measured prospectively in a standardized fashion up to 10 minutes, or until symptoms occurred, in all consecutive patients with syncope as a chief complaint presenting in the emergency department (ED) of a primary and tertiary care hospital. Patients unable to stand-up were excluded. Hypotension was considered to be the cause of syncope when there was: (1) a decrease in systolic blood pressure (SBP)or= 20 mm Hg with simultaneous symptoms; (2) a decrease in SBP between 10 and 20 mm Hg, but a SBPor= 90 mm Hg with or without symptoms; and (3) a nonsignificant decrease in SBP in the ED, but a prehospital valueor= 80 mm Hg was documented that prompted fluid therapy before standardized measurements. Among 788 patients with syncope seen in the ED during a 20-month period, 650 were included in the study, and 579 (89%) had standardized measurements of SBP. According to diagnostic criteria, orthostatic hypotension was considered to be the cause of syncope in 156 of them (24%). Fifty-eight patients (37%) had drug-induced hypotension, 33 (21%) hypovolemia, 19 (12%) postprandial hypotension, and 46 (29%) idiopathic hypotension. Asymptomatic SBP changesor= 20 mm Hg were found in 10% of patients with syncope attributed to other causes. Compared with patients with vasovagal disorder, those with orthostatic hypotension were older; had more comorbid conditions including hypertension, organic heart disease, and abnormal electrocardiogram; were taking more hypotensive medications; and required more frequently hospitalization (P.01). We concluded that standardized blood pressure measurement in the ED enabled to strongly implicate orthostatic hypotension as a cause of syncope in 24% of patients with this symptom. Drug-related hypotension was the most frequent cause for this disorder.