Gapless Electrocardiogram-Monitoring in stroke at high risk of atrial fibrillation.

BACKGROUND AND PURPOSE: Previous studies investigating prolonged electrocardiogram (ECG)-monitoring after ischemic stroke had significant gaps between the index event and the beginning of long-term monitoring. Atrial fibrillation (AF) detection might be higher if prolonged cardiac rhythm documentation is performed with a gapless approach without any interruption of monitoring time. METHODS: This investigator-initiated, prospective study included patients with acute ischemic stroke or transient ischemic attack at three study centers. Participants received gapless ECG-monitoring via telemetry during stroke-unit admission until implantation of an insertable cardiac monitor (ICM) within the first days after the index event. Patients acted as their own controls and also received standard 24-72-h Holter ECG. RESULTS: A total of 110 patients were included, of whom 86 (78.2%) had an embolic stroke of unknown source, 14 (12.7%) had small-vessel disease, and 10 (9.1%) had large-artery disease. AF was newly diagnosed in 17 (15.5%) patients via ICM monitoring, compared to one (0.9%) patient via Holter ECG during 6 months of follow-up (p < 0.001). The detection rate of AF within the first 30 days was 10.0%, which accounted for 64% of all new AF diagnoses. The median duration of the detected episodes was 1.7 (interquartile range = 0.2-4.7) h. All patients with new onset AF were treated with oral anticoagulation. CONCLUSIONS: Gapless ECG-monitoring is an effective strategy to significantly increase the detection rate of AF after ischemic stroke. This finding supports the use of long-term ECG-monitoring with a gapless approach without any interruption in monitoring time as the gold standard for clinical practice.

Sex difference in inappropriate therapy and survival among 1471 implantable cardioverter-defibrillator recipients.

INTRODUCTION: To assess a potential relationship between sex and outcome in recipients of an implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: All 1471 ICD recipients between 2000 and 2015 were sex-related analyzed with the following outcome parameters: overall survival (OS), the occurrence of inappropriate and appropriate antitachycardia pacing (ATP), and shock therapy. We followed 1206 (82%) male and 265 (18%) female ICD recipients during 4.1 ± 3.6 and 4.3 ± 3.8 years, respectively, (P = .369). Kaplan-Meier analysis revealed that there was no significant difference in OS between female and male patients (P = .132). After adjustment for relevant confounding factors in a multivariate model, sex remained a nonsignificant predictor of overall mortality (hazard ratio [male] = 1.11; P = .493). Negative binomial regression analysis revealed that women received less appropriate ATP therapy (rate ratio [RR] = 0.37; P = .043), whereas rates of appropriate shock therapy (RR = 1.95; P = .369) did not differ between women and men. No significant differences were observed in the occurrence of inappropriate ATP (RR = 1.22; P = .715) and inappropriate shock therapy (RR = 0.64; P = .121). CONCLUSION: Female and male patients equally benefit from ICD therapy in terms of OS. Women are less likely to receive appropriate ATP therapy, whereas appropriate shock and inappropriate ATP and shock therapy are independent of sex.

Defensive Implantable Cardioverter-Defibrillator Programming Is Safe and Reduces Inappropriate Therapy　- Comparison of 3 Programming Strategies in 1,471 Patients.

BACKGROUND: Careful device programming is necessary to reduce inappropriate antitachycardia pacing (ATP) and shock therapy in recipients of implantable cardioverter-defibrillators (ICD). This retrospective study investigated the safety and efficacy of a therapy-reducing programming strategy in comparison with conventional strategies in consecutive ICD recipients of a university cardiac center. Methods and Results: All 1,471 ICD recipients from 2000 to 2015 were analyzed. Individual ICD programming (IND) was used from 2000 to 2005 followed by standard-three-zone programming (STD) until 2010. From 2010 to 2015 therapy-reducing long detection time programming (RED) was established. The mean follow-up was 2.4±1.6, 2.3±1.6 and 1.7±1.2 years in the IND, STD and RED groups, respectively. Switchover from IND to STD revealed a significant reduction in inappropriate ATP (P=0.024) and shock therapy (P<0.001). Further reduction of 58% (RR=0.42, 95% confidence interval [CI]: 0.17-1.04; P=0.061) in inappropriate ATP and 29% (RR=0.71, 95% CI: 0.29-1.72; P=0.452) in inappropriate shock therapy was achieved by switchover from STD to RED. Kaplan-Meier analysis revealed a significant difference in time until first inappropriate ATP and shock therapy among the 3 groups, being lowest in the RED group (P≤0.001). There was no difference in overall mortality (P=0.416). CONCLUSIONS: Defensive ICD programming with prolonged detection times is safe and significantly reduced inappropriate ICD therapies.

Impact of an Ultra-Endurance Marathon on Cardiac Function in Association with Cardiovascular Biomarkers.

BACKGROUND: Participation in ultra-endurance races may lead to a transient decline in cardiac function and increased cardiovascular biomarkers. This study aims to assess alterations in biventricular function immediately and five days after the competition in relation to elevation of high-sensitivity cardiac Troponin I (hs-cTnI) and N-terminal-pro-brain-natriuretic-peptide (NT-proBNP). METHODS AND RESULTS: Fifteen participants of an ultramarathon (UM) with a running distance of 130 km were included. Transthoracic echocardiography and quantification of biomarkers was performed before, immediately after and five days after the race. A significant reduction in right ventricular fractional area change (FAC) was observed after the race (48.0 ± 4.6% vs. 46.7 ± 3.8%, p = 0.011) that persisted five days later (48.0 ± 4.6% vs. 46.3 ± 3.9%, p = 0.027). No difference in left ventricular ejection fraction (LVEF) was found (p = 0.510). Upon stratification according to biomarkers, participants with NT-proBNP above the median had a significantly reduced LVEF directly (60.8 ± 3.6% vs. 56.9 ± 4.8%, p = 0.030) and five days after the race (60.8 ± 3.6% vs. 55.3 ± 4.5%, p = 0.007) compared to baseline values. FAC was significantly reduced five days after the race (48.4 ± 5.1 vs. 44.3 ± 3.9, p = 0.044). Athletes with hs-cTnI above the median had a significantly reduced FAC directly after the race (48.1 ± 4.6 vs. 46.5 ± 4.4, p = 0.038), while no difference in LVEF was observed. No alteration in cardiac function was observed if hs-cTnI or NT-proBNP was below the median. CONCLUSION: A slight decline in cardiac function after prolonged strenuous exercise was observed in athletes with an elevation of hs-cTnI and NT-proBNP above the median but not below.

Antiplatelet Therapy and Anticoagulation before, during, and after Acute Coronary Syndrome.

Acute coronary syndrome (ACS) remains a major challenge in clinical practice, requiring rapid and effective antithrombotic treatment to mitigate adverse ischemic events while minimizing the risk of bleeding. In recent years, results from several clinical trials addressing this issue through various approaches have substantially improved the treatment landscape for patients presenting with ACS. The emergence of new, potent P2Y12 inhibitors has significantly enhanced thrombotic risk reduction and different strategies for de-escalating and shortening dual antiplatelet therapy (DAPT) have demonstrated promising outcomes in reducing bleeding rates. Furthermore, data from ongoing trials focusing on novel therapeutic agents and investigating alternative treatment strategies to optimize outcomes for ACS patients are expected in the next few years. In this review, we summarize the current knowledge and emphasize the critical role of individualized treatment approaches tailored to patient-specific risk factors and individual clinical scenarios.

Direct comparison of the diagnostic performance of growth differentiation factor 8 in pediatric versus adult heart failure.

INTRODUCTION: Growth differentiation factor 8 (GDF-8, myostatin) has been proposed for the management of adult heart failure (HF). Its potential role in pediatric HF patients is unknown. We sought to investigate its diagnostic performance in adult versus pediatric HF. METHODS: GDF-8 was measured prospectively in pediatric and adult HF patients and in matching controls. HF was defined as the combination of typical symptoms and impaired left ventricular systolic function. Diagnostic performance for the detection of HF was evaluated by receiver operating characteristic (ROC) analysis. RESULTS: We enrolled 137 patients with HF (85 pediatric) and 67 healthy controls (47 pediatric). Neither pediatric nor adult HF patients had significantly different GDF-8 levels compared to the reference groups (3.53 vs 3.46 ng/mL, p = 0.334, and 6.87 vs 8.15 ng/mL, p = 0.063, respectively), but pediatric HF patients had significantly lower GDF-8 levels compared to adult patients (p < 0.001). ROC analysis showed no significant improvement adding GDF-8 to NT-proBNP, age and sex (area under the curve (AUC): 0.870 vs 0.868, p = 0.614) in children and neither in addition to age nor sex in adult HF patients (AUC: 0.74 vs 0.62, p = 0.110). CONCLUSION: GDF-8 did not accurately differentiate between HF patients and normal comparators in neither adults nor in children.

Lipid-Lowering Therapy after Acute Coronary Syndrome.

Achieving guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets remains a significant challenge in clinical practice. This review assesses the barriers to reaching LDL-C goals and explores the potential solutions to these issues. When aiming for the recommended LDL-C goal, strategies like "lower is better" and "strike early and strong" should be used. The evidence supports the safety and efficacy of intensive lipid-lowering therapy post-acute coronary syndrome (ACS), leading to improved long-term cardiovascular health and atherosclerotic plaque stabilization. Despite the availability of effective lipid-lowering therapies, such as high-intensity statins, ezetimibe, the combination of both, bempedoic acid, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a substantial proportion of patients do not meet their LDL-C targets. Contributing factors include systemic healthcare barriers, healthcare provider inertia, patient non-adherence, and statin intolerance. Statin intolerance, often rather statin reluctance, is a notable obstacle due to perceived or expected side effects, which can lead to discontinuation of therapy. In conclusion, while there are obstacles to achieving optimal LDL-C levels post-ACS, these can be overcome with a combination of patient-centric approaches, clinical vigilance, and the judicious use of available therapies. The safety and necessity of reaching lower LDL-C goals to improve outcomes in patients post-ACS are well-supported by current evidence.

Low-density lipoprotein cholesterol reduction with immediate combination therapy of statin and ezetimibe compared to statin monotherapy after percutaneous coronary intervention.

BACKGROUND: Current guidelines recommend a stepwise initiation of lipid-lowering therapy after percutaneous coronary interventions (PCI) in treatment-naïve individuals. Patients might benefit from an earlier and stronger low-density lipoprotein-cholesterol (LDL-C) reduction through upfront combination therapies. METHODS: This retrospective study included patients without previous lipid-lowering therapy undergoing acute or elective PCI with stent implantation between January 2016 and December 2019. Patients initiated on statin monotherapy vs. a combination of statin and ezetimibe were compared. The primary endpoint was an LDL­C reduction into the target range of < 55 mg/dL at 3 months. The secondary endpoint was the occurrence of major cardiovascular events (MACE). RESULTS: A total of 204 lipid-lowering therapy naive patients were included, of whom 157 (77.0%) received statin monotherapy and 47 (23.0%) combination therapy. Median LDL­C levels were higher in patients initiated on combination therapy vs. monotherapy (140 mg/dL, interquartile range, IQR, 123-167 mg/dL vs. 102 mg/dL, IQR 80-136 mg/dL, p < 0.001). The LDL­C reduction was greater in patients treated with combination therapy vs. statin monotherapy (-73 mg/dL, -52.1% vs. -43 mg/dL, -42.2%, p < 0.001). While the primary endpoint was similar between groups (44.7% vs. 36.1%, p = 0.275), combination therapy significantly increased the proportion of patients achieving the treatment target in the presence of an admission LDL-C > 120 mg/dL (46.2% vs. 26.2%, p = 0.031). The rates of MACE were similar between the two groups (10.6% vs. 17.8%, p = 0.237) at a median follow-up of 2.2 years, IQR 1.46-3.10 years. CONCLUSION: Immediate initiation of high-intensity statin and ezetimibe treatment might be considered as the default strategy in treatment-naïve patients with high admission LDL­C undergoing PCI.

Association of Interleukin-32 and Interleukin-34 with Cardiovascular Disease and Short-Term Mortality in COVID-19.

BACKGROUND: Excess cardiovascular (CV) morbidity and mortality has been observed in patients with COVID-19. Both interleukin-32 (IL-32) and interleukin-34 (IL-34) have been hypothesized to contribute to CV involvement in COVID-19. METHODS: This prospective, observational study of patients with laboratory-confirmed COVID-19 infection was conducted from 6 June to 22 December 2020 in a tertiary care hospital in Vienna, Austria. IL-32 and IL-34 levels on admission were collected and tested for their association with CV disease and short-term mortality in patients with COVID-19. CV disease was defined by the presence of coronary artery disease, heart failure, stroke or atrial fibrillation and patients were stratified by CV disease burden. RESULTS: A total of 245 eligible patients with COVID-19 were included, of whom 37 (15.1%) reached the primary endpoint of 28-day mortality. Of the total sample, 161 had no CV disease (65.7%), 69 had one or two CV diseases (28.2%) and 15 patients had ≥three CV diseases (6.1%). Median levels of IL-32 and IL-34 at admission were comparable across the three groups of CV disease burden. IL-32 and IL-34 failed to predict mortality upon both univariable and multivariable Cox regression analysis. The two CV disease groups, however, had a significantly higher risk of mortality within 28 days (one or two CV diseases: crude HR 4.085 (95% CI, 1.913-8.725), p < 0.001 and ≥three CV diseases: crude HR 13.173 (95% CI, 5.425-31.985), p < 0.001). This association persisted for those with ≥three CV diseases after adjustment for age, gender and CV risk factors (adjusted HR 3.942 (95% CI, 1.288-12.068), p = 0.016). CONCLUSION: In our study population of hospitalized patients with COVID-19, IL-32 and IL-34 did not show any associations with CV disease or 28-day mortality in the context of COVID-19. Patients with multiple CV diseases, however, had a significantly increased risk of short-term mortality.

New Treatment Targets and Innovative Lipid-Lowering Therapies in Very-High-Risk Patients with Cardiovascular Disease.

The effective and fast reduction of circulating low-density lipoprotein cholesterol (LDL-C) is a cornerstone for secondary prevention of atherosclerotic disease progression. Despite the substantial lipid-lowering effects of the established treatment option with statins and ezetimibe, a significant proportion of very-high-risk patients with cardiovascular disease do not reach the recommended treatment goal of <55 mg/dL (<1.4 mmol/L). Novel lipid-lowering agents, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies alirocumab and evolocumab, the small interfering ribonucleotide acid (si-RNA) inclisiran, as well as the recently approved bempedoic acid, now complete the current arsenal of LDL-C lowering agents. These innovative therapies have demonstrated promising results in clinical studies. Besides a strong reduction of LDL-C by use of highly effective agents, there is still discussion as to whether a very rapid achievement of the treatment goal should be a new strategic approach in lipid-lowering therapy. In this review, we summarize evidence for the lipid-modifying properties of these novel agents and their safety profiles, and discuss their potential pleiotropic effects beyond LDL-C reduction (if any) as well as their effects on clinical endpoints as cardiovascular mortality. In addition to a treatment strategy of "the lower, the better", we also discuss the concept of "the earlier, the better", which may also add to the early clinical benefit of large LDL-C reduction after an acute ischemic event.

Biomarkers Associated with Cardiovascular Disease in COVID-19.

Coronavirus disease-19 (COVID-19) emerged late December 2019 in the city of Wuhan, China and has since spread rapidly all over the world causing a global pandemic. While the respiratory system is the primary target of disease manifestation, COVID-19 has been shown to also affect several other organs, making it a rather complex, multi-system disease. As such, cardiovascular involvement has been a topic of discussion since the beginning of the COVID-19 pandemic, primarily due to early reports of excessive myocardial injury in these patients. Treating physicians are faced with multiple challenges in the management and early triage of patients with COVID-19, as disease severity is highly variable ranging from an asymptomatic infection to critical cases rapidly deteriorating to intensive care treatment or even fatality. Laboratory biomarkers provide important prognostic information which can guide decision making in the emergency department, especially in patients with atypical presentations. Several cardiac biomarkers, most notably high-sensitive cardiac troponin (hs-cTn) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), have emerged as valuable predictors of prognosis in patients with COVID-19. The purpose of this review was to offer a concise summary on prognostic cardiac biomarkers in COVID-19 and discuss whether routine measurements of these biomarkers are warranted upon hospital admission.

ST-T segment changes in prehospital emergency physicians in the field: a prospective observational trial.

AIMS: Due to time-critical decision-making, physical strain and the uncontrolled environment, prehospital emergency management is frequently associated with high levels of stress in medical personnel. Stress has been known to cause ischemia like changes in electrocardiograms (ECGs), including arrhythmias and deviations in ST-T segments. There is a lack of knowledge regarding the occurrence of changes in ST-T segments in prehospital emergency physicians. We hypothesized that ST-T segment deviations occur in prehospital emergency physicians in the field. METHODS: In this prospective observational trial, ST-T segments of emergency physicians were recorded using 12-lead Holter ECGs. The primary outcome parameter was defined as the incidence of ST-T segment changes greater than 0.1 mV in two corresponding leads for more than 30 s per 100 rescue missions. The secondary outcomes included T-wave inversions and ST-segment changes shorter than 30 s or smaller than 0.1 mV. Surrogate parameters of stress were measured using the NASA-Task Load Index and cognitive appraisal, and their correlation with ST-T segment changes were also assessed. RESULTS: Data from 20 physicians in 36 shifts (18 days, 18 nights) including 208 missions were analysed. Seventy percent of previously healthy emergency physicians had at least one ECG abnormality; the mean duration of these changes was 30 s. Significantly more missions with ECG changes were found during night than day shifts (39 vs. 17%, p < 0.001). Forty-nine ECG changes occurred between missions. No ST-T segment changes > 30 s and > 0.1 mV were found. Two ST-T segment changes < 30 s or < 0.1 mV (each during missions) and 122 episodes of T-wave inversions (74 during missions) were identified. ECG changes were found to be associated with alarms when asleep and NASA task load index. CONCLUSION: ECG changes are frequent and occur in most healthy prehospital emergency physicians. Even when occurring for less than 30 s, such changes are important signs for high levels of stress. The long-term impact of these changes needs further investigation. Trial registration The trial was registered at ClinicalTrials.gov (NCT04003883) on 1.7.2019:  https://clinicaltrials.gov/ct2/show/NCT04003883?term=emergency+physician&rank=2.

Short dual antiplatelet therapy and dual antiplatelet therapy de-escalation after primary percutaneous intervention: For whom and how.

Dual antiplatelet therapy (DAPT) for 6-12 months, followed by lifelong aspirin monotherapy is considered an effective standard therapy for the prevention of thrombo-ischemic events in patients with acute and chronic coronary syndrome (ACS, CCS) undergoing percutaneous coronary intervention (PCI) or after a primarily conservative treatment decision. In ACS patients, the stronger P2Y12-inhibitors ticagrelor or prasugrel are recommended in combination with aspirin unless the individual bleeding risk is high and shortening of DAPT is warranted or clopidogrel is preferred. However, also in patients at low individual bleeding risk, DAPT is associated with a higher risk of bleeding. In recent years, new antithrombotic treatment strategies, such as shortening DAPT followed by early P2Y12-inhibitor monotherapy and de-escalating DAPT from potent P2Y12-inhibitors to clopidogrel by maintaining DAPT duration time, have been investigated in clinical trials and shown to reduce bleeding complications in cardiovascular high-risk patients without negative effects on ischemic events. In this review, we summarize the current knowledge and discuss its implication on future antithrombotic strategies in terms of a personalized medicine.

Is diversity harmful?-Mixed-brand cardiac implantable electronic devices undergoing magnetic resonance imaging.

BACKGROUND: Many patients with cardiac implantable electronic devices (CIED) undergo magnetic resonance imaging (MRI); however, a relevant proportion have a CIED system that has not been classified as MRI-conditional because of generators and leads from different brands (mixed-brand group). The available data concerning the outcome of these mixed patients undergoing MRI is limited. METHODS: A retrospective single center study, including all patients with CIEDs undergoing MRI between January 2013 until May 2020, was performed. Primary endpoints were defined as death or any adverse event necessitating hospitalization or CIED revision. Secondary endpoints were the occurrence of any sign for beginning device or lead failure or patient discomfort during MRI. RESULTS: A total of 227 MRI examinations, including 10 thoracic MRIs, were carried out in 158 patients, with 1-9 MRIs per patient. Of the patients 38 underwent 54 procedures in the mixed-brand group and 89 patients underwent 134 MRIs in the MRI-conditional group. Of the patients 31 were excluded since the MRI conditionality could not be determined. No primary endpoints occurred within the mixed-brand group but in 2.2% of the MRI-conditional group (p = 1.000), with 2 patients developing new atrial fibrillation during MRI, of whom one additionally had a transient CIED dysfunction. No secondary endpoints were met in the mixed-brand group compared to 3.4% in the MRI-conditional group (p = 0.554). No complications occurred in the excluded patients. CONCLUSION: The complication rate of CIED patients undergoing MRI was low. Patients with a mixed CIED system showed no signs of increased risk of adverse events compared to patients with MRI-conditional CIED systems.

Direct cardiovascular complications and indirect collateral damage during the COVID-19 pandemic : A review.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), puts a heavy strain on healthcare systems around the globe with high numbers of infected patients. Pre-existing cardiovascular disease is a major risk factor for a severe clinical course of COVID-19 and is associated with adverse outcome. COVID-19 may directly exacerbate underlying heart disease and is frequently aggravated by cardiovascular complications, including arterial and venous thromboembolic events, malignant arrhythmia and myocardial injury. In addition to these direct cardiac manifestations of COVID-19, patients with cardiovascular disease face further indirect consequences of the pandemic, as the respective resources in the healthcare systems need to be redirected to cope with the high numbers of infected patients. Consecutively, a substantial decrease in cardiac procedures was reported during the pandemic with lower numbers of coronary angiographies and device implantations worldwide. As a consequence an increased number of out-of-hospital cardiac arrests, late-comers with subacute myocardial infarction and of patients presenting in cardiogenic shock or preshock were observed. Maintenance of high-quality cardiac care by avoiding a reduction of cardiac services is of utmost importance, especially in times of a pandemic.

Appropriate and inappropriate therapy in patients with single- or multi-chamber implantable cardioverter-defibrillators.

BACKGROUND: Inappropriate ICD therapy is associated with adverse outcome. Previous studies indicated that patients with a cardiac resynchronization therapy-defibrillator (CRT-D) might have a lower risk for inappropriate device activations than patients with a single (VVI) or dual chamber (DDD) ICD. METHODS: All ICD recipients from a university cardiac center between 2000 - 2015 were included in this analysis. Outcome parameters were incidence of appropriate and inappropriate therapy and overall mortality. RESULTS: A total of 1471 patients were analyzed: 629 (43%) patients with a VVI-ICD, 486 (33%) patients with a DDD-ICD and 356 (24%) with a CRT-D device. During an average follow-up of 4.1 ± 3.6 years, CRT-D patients had the lowest risk to receive at least one inappropriate shock therapy (p < 0.001). Rates of appropriate (RR (Rate Ratio) = 0.45, p = 0.019) and inappropriate shock therapy (RR = 0.38, p = 0.021) were significantly lower in CRT-D patients compared to VVI-patients. CRT-D recipients had a lower rate of appropriate shock therapy (RR = 0.323, p = 0.043) compared to DDD patients, but not of inappropriate shock therapy (p = 0.371). Kaplan Meier Analysis did not reveal a significant difference in overall survival (p = 0.396). However, after adjustment for relevant confounding factors, VVI-patients had a higher risk for overall-death (HR = 1.28, p = 0.030). CONCLUSIONS: CRT-D recipients have a significantly lower rate of appropriate shock therapy and a lower rate of inappropriate shock therapy. More frequent inappropriate therapies in VVI-ICD recipients may account for their higher overall mortality.

Importance of Diastolic Function for the Prediction of Arrhythmic Death: A Prospective, Observer-Blinded, Long-Term Study.

BACKGROUND: Patients with ischemic or dilated cardiomyopathy and reduced left ventricular ejection fraction (LVEF) face a high risk for ventricular arrhythmias. Exact grading of diastolic function might improve risk stratification for arrhythmic death. METHODS: We prospectively enrolled 120 patients with ischemic, 60 patients with dilated cardiomyopathy, and 30 patients with normal LVEF. Diastolic function was graded normal (N) or dysfunction grade I to III. Primary outcome parameter was arrhythmic death (AD) or resuscitated cardiac arrest (RCA). RESULTS: Normal diastolic function was found in 23 (11%) patients, dysfunction grade I in 107 (51%), grade II in 31 (14.8%), and grade III in 49 (23.3%) patients, respectively. After an average follow-up of 7.0±2.6 years, AD or RCA was observed in 28 (13.3%) and 33 (15.7%) patients, respectively. Nonarrhythmic death was found in 41 (19.5%) patients. On Kaplan-Meier analysis, patients with dysfunction grade III had the highest risk for AD or RCA (P<0.001). This finding was independent from the degree of LVEF dysfunction and was observed in patients with LVEF≤35% (P=0.001) and with LVEF>35% (P=0.014). Nonarrhythmic mortality was the highest in patients with dysfunction grade III. This was true for patients with LVEF≤35% (P=0.009) or >35% (P<0.001). In an adjusted model for relevant confounding factors, grade III dysfunction was associated with a 3.5-fold increased risk for AD or RCA in the overall study population (hazard ratio=3.52; P<0.001). CONCLUSIONS: Diastolic dysfunction is associated with a high risk for AD or RCA regardless if LVEF is ≤35% or >35%. Diastolic function grading might improve risk stratification for AD.

Elevated plasma levels of asymmetric dimethylarginine and the risk for arrhythmic death in ischemic and non-ischemic, dilated cardiomyopathy - A prospective, controlled long-term study.

INTRODUCTION: Elevated plasma levels of asymmetric dimethylarginine (ADMA), an inhibitor of NO synthase, are associated with adverse outcome. There is no data available, whether ADMA levels are associated with arrhythmic death (AD) in patients with ischemic cardiomyopathy (ICM) or non-ischemic, dilated cardiomyopathy (DCM). METHODS AND RESULTS: A total of 110 ICM, 52 DCM and 30 control patients were included. Primary outcome parameter of this prospective study was arrhythmic death (AD) or resuscitated cardiac arrest (RCA). Plasma levels of ADMA were significantly higher in ICM (p < 0.001) and in DCM (p < 0.001) patients compared to controls. During a median follow-up of 7.0 years, 62 (32.3%) patients died. AD occurred in 26 patients and RCA was observed in 22 patients. Plasma levels of ADMA were not associated with a significantly increased risk of AD or RCA in ICM (hazard ratio (HR) = 1.37, p = 0.109) or in DCM (HR = 1.06, p = 0.848) patients. No significant association was found with overall mortality in ICM (HR = 1.39, p = 0.079) or DCM (HR = 1.10, p = 0.666) patients. Stratified Kaplan-Meier curves for ADMA levels in the upper tertile (>0.715 µmol/l) or the two lower tertiles (≤0.715 µmol/l) did not show a higher risk for AD or RCA (p = 0.221) or overall mortality (p = 0.548). In patients with left ventricular ejection fraction ≤ 35%, ADMA was not associated with AD or RCA (HR = 1.35, p = 0.084) or with overall mortality (HR = 1.24, p = 0.162). CONCLUSIONS: Plasma levels of ADMA were elevated in patients with ICM or DCM as compared to controls, but were not significantly predictive for overall mortality or the risk for arrhythmic death.