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.

Comparison of burst versus ramp antitachycardia pacing therapy for ventricular tachycardia: A meta-analysis.

Current guidelines recommend at least one attempt of defibrillator antitachycardia pacing (ATP) therapy, showing preference for burst therapy. The objective of this study is to compare ramp versus burst ATP therapy proportion of success and acceleration in treating spontaneous or induced ventricular tachycardia (VT). The review protocol was previously published in PROSPERO. Data synthesis and measures of heterogeneity (I2 ) was performed by CMA® software v.3 comparing proportions in both groups. Sensitivity analysis was performed as subgroup or meta-regression according to quality, clinical characteristics, and differences in design. Thirteen studies including 30,117 VT episodes in 1672 patients were analyzed. There was no significant difference in the proportion of success between burst and ramp therapy in spontaneous VT (odds ratio = 1.116; 95% confidence interval [CI] = 0.788-1.579; I2 = 89%). There was no significant difference in the proportion of success between burst and ramp therapy in induced VT (odds ratio = 0.820; 95% CI = 0.468-1.437; I2 = 93%). No significant difference was found in the proportion of acceleration between burst and ramp in spontaneous VT (odds ratio = 0.792; 95% CI = 0.476-1.317; I2 = 83%). No significant difference was found in the proportion of acceleration between burst and ramp in induced VT (odds ratio = 1.234; 95% CI = 0.802-1.898; I2 = 55%). Sensitivity analysis did not change main results. There is no difference in success or in acceleration proportion between burst or ramp ATP therapy irrespective if the VT was spontaneous or induced. Future implantable cardioverter defibrillator programming guidelines should offer both ATP therapies without preference in one of them.

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.

GDF-15 is a better complimentary marker for risk stratification of arrhythmic death in non-ischaemic, dilated cardiomyopathy than soluble ST2.

Growth differentiation factor (GDF)-15 and soluble ST2 (sST2) are established prognostic markers in acute and chronic heart failure. Assessment of these biomarkers might improve arrhythmic risk stratification of patients with non-ischaemic, dilated cardiomyopathy (DCM) based on left ventricular ejection fraction (LVEF). We studied the prognostic value of GDF-15 and sST2 for prediction of arrhythmic death (AD) and all-cause mortality in patients with DCM. We prospectively enrolled 52 patients with DCM and LVEF ≤ 50%. Primary end-points were time to AD or resuscitated cardiac arrest (RCA), and secondary end-point was all-cause mortality. The median follow-up time was 7 years. A cardiac death was observed in 20 patients, where 10 patients had an AD and 2 patients had a RCA. One patient died a non-cardiac death. GDF-15, but not sST2, was associated with increased risk of the AD/RCA with a hazard ratio (HR) of 2.1 (95% CI = 1.1-4.3; P = .031). GDF-15 remained an independent predictor of AD/RCA after adjustment for LVEF with adjusted HR of 2.2 (95% CI = 1.1-4.5; P = .028). Both GDF-15 and sST2 were independent predictors of all-cause mortality (adjusted HR = 2.4; 95% CI = 1.4-4.2; P = .003 vs HR = 1.6; 95% CI = 1.05-2.7; P = .030). In a model including GDF-15, sST2, LVEF and NYHA functional class, only GDF-15 was significantly associated with the secondary end-point (adjusted HR = 2.2; 95% CI = 1.05-5.2; P = .038). GDF-15 is superior to sST2 in prediction of fatal arrhythmic events and all-cause mortality in DCM. Assessment of GDF-15 could provide additional information on top of LVEF and help identifying patients at risk of arrhythmic death.

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.

Risk of arrhythmic death in ischemic heart disease: a prospective, controlled, observer-blind risk stratification over 10 years.

BACKGROUND: Risk of arrhythmic death is considered highest in ischemic heart disease with severe left ventricular ejection fraction (LVEF) reduction. Non-invasive testing should improve decision-making of prophylactic defibrillator (ICD) implantation. DESIGN: We enrolled 120 patients with ischemic heart disease and LVEF < 50% and 30 control subjects without ischemic heart disease and normal LVEF. An initial assessment, a second assessment after 3 years and a final follow-up comprised of pharmacological baroreflex testing (BRS), short-term spectral [low-frequency (LF) to high-frequency (HF) ratio] and long-term time-domain analysis of heart rate variability (SDNN), exercise Microvolt T-wave alternans (MTWA) and others. RESULTS: The median follow-up was 7·5 years. Resuscitated cardiac arrest and arrhythmic death due to ventricular arrhythmias ≥ 240/min was observed in 18% and 15% of patients, respectively. Cardiac death was observed in 28% of patients. The incidence of arrhythmic death and resuscitated cardiac arrest was identical in patients with ischemic heart disease with LVEF < 30% and ≥ 30%. No significant difference between subgroups with LVEF of < 30%, 30-39% and ≥ 40% was found either. MTWA, BRS, SDNN and LF to HF ratio failed to identify patients at risk of arrhythmic death in a multiple regression model. CONCLUSIONS: Ischemic heart disease patients with LVEF < 30% and ≥ 30% face the same risk of arrhythmic death. Stratification techniques fail to identify high-risk patients. Therefore, the current practice to constrain prophylactic ICDs to patients with severely reduced LVEF seems to be insufficient.

T-wave variability for the prediction of fast ventricular arrhythmias ­ prospective, observer-blind study.

BACKGROUND: The clinical value of T-wave variability (T-var) for ventricular arrhythmia (VA) risk prediction was evaluated. METHODS AND RESULTS: Three 20-min Holter-ECG-based T-var measurements (I1 at baseline, I2 after 6.5 ± 1.6 months and I3 after 13.1 ± 2.0 months) were done in 121 patients. T-var was defined as the amplitude variability of the T-wave with the maximum of T-wave oscillation. The endpoint was a fast, potentially fatal VA (>240 beats/min). During follow-up (20 ± 4 months) 20/121 patients (55% ischemic heart disease, 15% preserved left ventricular ejection fraction [LVEF]) had fast VA terminated by ICD or external shock. Although T-var did not differ between patients with vs. without fast VA at baseline (I1: 10.7 ± 7.3 µV vs. 7.8 ± 4.1 µV, P=0.170), patients with fast VA had higher T-var compared to those without fast VA at 2 subsequent measurements (I2: 14.0 ± 6.5 µV vs. 8.2 ± 3.6 µV, P=0.030; I3: 17.0 ± 5.4 µV vs. 8.8 ± 4.6 µV, P=0.004). The increase in T-var between I1 and I2 was higher in patients with fast VA (∆T-var=7.0 ± 9.3 µV), as compared to patients without (∆T-var=0.4 ± 4.3 µV). After adjustment for LVEF in a multiple logistic regression model, the odds ratio for developing fast VA was 1.1 (P=0.056) for each 1-µV increment in T-var at I1. CONCLUSIONS: T-var is elevated in patients with fast VA, and both elevation of T-var and increase in T-var may complement LVEF in VA risk stratification.

Primary preventive cardioverter-defibrillator implantation (Pro-ICD) in patients awaiting heart transplantation. A prospective, randomized, controlled 12-year follow-up study.

The aim of this study was to evaluate whether short-term primary preventive cardioverter-defibrillator (ICD) implantation as bridge to heart transplantation (HTX) provides any survival benefit. Thirty-three patients awaiting HTX were randomized to either conventional therapy (control group) or primary preventive ICD implantation (ICD group). Fourteen patients had ischemic cardiomyopathy (ICM) and 19 patients had dilated cardiomyopathy (DCM). Sixteen patients were randomized to the ICD group and 17 patients were randomized to the control group. Twenty patients (61%) were transplanted after a waiting time of 10 ± 9 months. The remaining 13 patients (39%) were not transplanted because of clinical improvement (n = 5), cerebral hemorrhage (n = 3), or death (n = 5). On the waiting list, 3 ICD patients with DCM developed slow VTs without ICD intervention, two patients with ICM (6%) had fast VT terminated by the ICD, and no arrhythmic death was observed. After 11.9 years (median), 13 of 20 HTX patients (65%) and 5 of 13 non-HTX patients (38%) were alive. Survivors had a higher LVEF (22 ± 6 vs. 17 ± 4%, P = 0.0092) and a better exercise capacity (75 ± 29 vs. 57 ± 24 Watt, P = 0.0566) at baseline as compared to nonsurvivors. This study may not support the general use of primary preventive ICDs as a short-term bridge to heart transplantation.

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.

ECG Smart Monitoring versus Implantable Loop Recorders for Atrial Fibrillation Detection after Cryptogenic Stroke-An Overview for Decision Making.

Up to 20% of patients with ischemic stroke or transient ischemic attack have a prior history of known atrial fibrillation (AF). Additionally, unknown AF can be detected by different monitoring strategies in up to 23% of patients with cryptogenic or non-cardioembolic stroke. However, most studies had substantial gaps in monitoring time, especially early after the index event. Following this, AF rates would be higher if patients underwent continuous monitoring early after stroke, avoiding any gaps in monitoring. The few existing randomized studies focused on patients with cryptogenic stroke but did not focus otherwise specifically on prevention strategies in patients at high risk for AF (patients at higher age or with high CHA2DS2-VASC scores). Besides invasive implantable loop recorders (ILRs), external loop recorders (ELRs) and mobile cardiac outpatient telemetry (MCOT) are non-invasive tools that are commonly used for long-term ECG monitoring in cryptogenic-stroke patients in the ambulatory setting. The role of MCOT and hand-held devices within ECG smart monitoring in the detection of AF for the prevention of and after cryptogenic stroke is currently unclear. This intense review provides an overview of current evidence, techniques, and gaps in knowledge and aims to advise which patients benefit most from the current available devices.

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.

New-generation miniaturized insertable cardiac monitor with a long sensing vector: Insertion procedure, sensing performance, and home monitoring transmission success in a real-world population.

Background: Insertable cardiac monitors (ICMs) require an invasive procedure and are used for purely diagnostic purposes. Therefore, simplicity of the insertion procedure, low complication rate, long-term patient acceptance, sensing quality, and reliable remote monitoring are of great importance. Objective: To evaluate a novel ICM (BIOMONITOR III) regarding all these aspects. Methods: BIOMONITOR III has a miniaturized profile, long sensing vector (≈70 mm), a fast insertion tool for pocket formation and ICM placement in 1 step, and daily automatic Home Monitoring (HM) function. We evaluated the insertion procedure, complication rate, patient acceptance, sensing quality, and HM performance in 653 patients with BIOMONITOR III inserted for any ICM indication within 2 ongoing studies involving 51 sites in 11 countries. Results: The median time from skin incision to wound closure was 4.0 minutes (interquartile range, 2.3-6.2 minutes). Median follow-up period was 274 days (interquartile range, 175-342 days). Serious adverse device-related events occurred in 6 patients (0.9%). No deep infections were reported in 334 patients without antibiotic prophylaxis. The wearing comfort was good or excellent in ≈95%. The mean R-wave amplitude (0.73 mV) and HM transmission rate (≈94% of days) were stable over 1.5 years. R-wave amplitudes were larger (mean 0.80 vs 0.62 mV, P < .001) and noise burden was lower (median 3.7 vs 14.5 minutes/day, P < .001) for ICM insertions parallel to the heart's long axis (54.2%) vs parasternal (41.3%). A gross visibility of P waves was 95.1%. Conclusion: The study demonstrated fast insertion times, low complication rate, high patient acceptance, and favorable long-term sensing and HM performance of the ICM.

Fitness to Drive After Syncope and/or in Cardiovascular Disease - An Overview and Practical Advice.

The risk of syncope occurring while driving has implications for personal and public safety. Little is thought about the medical considerations related to the driving of motor vehicles. Physicians treating patients with cardiovascular disease need to acquire basic competences to be able to advise them about their fitness to drive. Current knowledge, governmental regulations, and recommendations concerning fitness to drive in patients with syncope and/or cardiovascular disease are presented. Narrative review with educational and clinical advice. Cardiovascular disease can make a driver lose control of a vehicle without warning and thereby lead to an accident. The main pathophysiological mechanisms of sudden loss of control are disturbances of brain perfusion (eg, syncope with or without cardiac arrhythmia, sudden cardiac death due to ventricular fibrillation or asystole, stroke, etc.) and marked general weakness (eg, after major surgery or in heart failure). Patients with syncope and/or cardiovascular disease should be properly advised by their physicians about their fitness to drive, and restrictions should be documented.

Pacemaker lead-associated tricuspid regurgitation in patients with or without pre-existing right ventricular dilatation.

BACKGROUND: Transcatheter tricuspid valve intervention became an option for pacemaker lead-associated tricuspid regurgitation. This study investigated the progression of tricuspid regurgitation (TR) in patients with or without pre-existing right ventricular dilatation (RVD) undergoing pacemaker implantation. METHODS: Patients were included if they had implantation of transtricuspid pacemaker lead and completed echocardiography before and after implantation. The cohort was divided in patients with and without RVD (cut-off basal RV diameter ≥ 42 mm). TR was graded in none/mild, moderate, and severe. Worsening of one grade was defined as progression. Survival analyses were plotted for 10 years. RESULTS: In total, 990 patients were analyzed (24.5% with RVD). Progression of TR occurred in 46.1% of patients with RVD and in 25.6% of patients without RVD (P < 0.001). Predictors for TR progression were RV dilatation (OR 2.04; 95% CI 1.27-3.29; P = 0.003), pre-existing TR (OR 4.30; 95% CI 2.51-7.38; P < 0.001), female sex (OR 1.68; 95% CI 1.16-2.43; P = 0.006), single RV lead (OR 1.67; 95% CI 1.09-2.56; P = 0.018), mitral regurgitation (OR 2.08; 95% CI 1.42-3.05; P < 0.001), and enlarged left atrium (OR 1.98; 95% CI 1.07-3.67; P = 0.03). Survival-predictors were pacemaker lead-associated TR (HR 1.38; 95% CI 1.04-1.84; P = 0.028), mitral regurgitation (HR 1.34; 95% CI 1.02-1.77; P = 0.034), heart failure (HR 1.75; 95% CI 1.31-2.33; P < 0.001), kidney disease (HR 1.62; 95% CI 1.25-2.11; P < 0.001), and age ≥ 80 years (HR 2.84; 95% CI 2.17-3.71; P < 0.001). CONCLUSIONS: Patients with RVD receiving pacemaker suffered from increased TR progression, leading to decreased survival.

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.

Cardiac Autonomic Dysfunction in Multiple Sclerosis: A Systematic Review of Current Knowledge and Impact of Immunotherapies.

Cardiac autonomic dysfunction (CAD) has been reported in patients with multiple sclerosis (MS). This systematic review summarizes the evidence for the types and prevalence of CAD in MS patients, as well as its association with MS type, disease characteristics, fatigue and immunotherapies used to treat MS. The analysis revealed that CAD is correlated with pathophysiological processes of MS, can trigger serious cardiovascular complications that may reduce life expectancy, and may have implications for treatment with immunotherapies, especially fingolimod. Numerous mainly small case-control or cohort studies have reported various measures of CAD (particularly heart rate variation) in MS patients, showing higher rates of abnormality versus controls. A smaller number of studies have reported on cardiac autonomic symptoms in MS, including orthostatic intolerance/dizziness in around 50% of patients. CAD also appears to be associated with disease duration and to be more common in progressive than relapsing-remitting MS. However, although a substantial evidence base suggests that assessing CAD in people with MS may be important, standardised methods to evaluate CAD in these patients have not yet been established. In addition, no studies have yet looked at whether treating CAD can reduce the burden of MS symptoms, disease activity or the rate of progression.

Sex Differences and Long-Term Outcome in Patients With Pacemakers.

Introduction: Evidence of sex-related differences in patients with pacemakers regarding comorbidities is insufficiently investigated. The aim of this study was to determine the relationship of cardiovascular comorbidities and sex category with properties of pacemaker implantation, pacemaker follow-up, and long-term survival. Methods: This retrospective, single-center cohort study consisted of 6,362 pacemaker-patients (39.7% female) enrolled between May 2000 and April 2015. Functional pacemaker parameters were registered at regular pacemaker controls. Survival status and cause of death were analyzed in relation to comorbidities, implanted pacing devices, and echocardiography. Survival analyses were plotted for a 10-year follow-up. Results: Patients with hypertension or hyperlipidemia had higher rates of implantations due to sick sinus syndrome (28.6 vs. 25.5% without hypertension, P < 0.001; 30.7 vs. 25.7% without hyperlipidemia, P < 0.001), while endocarditis was associated with higher rates of implantations due to AV block (46.7 vs. 33.4%, P < 0.001). Patients with valvular heart disease had higher rates of pacemaker implantation due to bradycardic atrial fibrillation (24.9 vs. 21.0% without valvular heart disease, P < 0.001). Ventricular pacing threshold increased in both sexes during the follow-up and was higher in women in the final follow-up (0.94 vs. 0.91 V in men, P = 0.002). During the 10-years follow-up, 6.1% of women and 8.6% of men underwent lead replacement (P = 0.054). Device and lead replacement rates were increased if the comorbidities coronary artery disease, heart failure, hypertension, hyperlipidemia, valvular heart disease, previous stroke/TIA, atrial arrhythmias, chronic kidney disease, or endocarditis were present. Diabetes and previous CABG increase the rates of device replacement, but not the rate of lead replacement. Severe tricuspid regurgitation after implantation of pacemaker was present in more men than women (14.4 vs. 6.1%, P < 0.001). In a multivariate COX regression, the following variables were associated with independent decrease of 10-year survival: hypertension (HR 1.34, 95% CI 1.09-1.64), chronic kidney disease (HR 1.83, 95% CI 1.53-2.19), tricuspid regurgitation after pacemaker implantation (HR 1.48, 95% CI 1.26-1.74). Survival was independently increased in female sex (HR 0.83, 95% CI 0.70-0.99) and hyperlipidemia (HR 0.81, 95% CI 0.67-0.97). Conclusions: Cardiovascular comorbidities influenced significantly pacemaker implantations and long-term outcome. Trial Registration: ClinicalTrials.gov Unique identifier: NCT03388281.

Ventricular tachycardia in arrhythmogenic right ventricular dysplasia/cardiomyopathy: clinical presentation, risk stratification and results of long-term follow-up.

BACKGROUND: Not all patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) are at risk for sudden cardiac death. The aim of the study was to evaluate the risk stratification in patients with ARVD/C. METHODS AND RESULTS: Programmed ventricular stimulation (PVS) was performed in 34 ARVD/C patients. Twenty-two, 7 and 4 patients had documented sustained monomorphic ventricular tachycardia (smVT), non-smVT and ventricular fibrillation, respectively. One patient experienced syncope only. An implantable cardioverter defibrillator (ICD) was implanted in 11 patients inducible in smVT with hemodynamic compromise, in 4 patients with documented ventricular fibrillation and in one patient with non-smVT (194 ms tachycardia cycle length) (ICD group, n = 16). Ten patients were left without any antiarrhythmic therapy, 5 patients received antiarrhythmic drugs and 3 patients underwent successful VT ablation (non-ICD group, n = 18). Thirteen patients had an abnormal signal averaged ECG. During 6.5 +/- 2.4 years 69% of ICD patients received appropriate discharges and one non-ICD patient had a hemodynamically tolerated smVT recurrence (no sudden cardiac death in both groups). Comparison between the cycle lengths of clinical VT, induced VT and follow-up VT revealed a strong relationship (R = 0.62-0.88). On multivariate analysis abnormal signal averaged ECG and decreased left ventricular ejection fraction were statistically significant predictors for VT recurrence. CONCLUSIONS: In ARVD/C the tachycardia cycle length of clinical VT, PVS-induced VT and follow-up VT correlate well implicating that a PVS-guided approach does not provide additional information. Spontaneous arrhythmia in combination with clinical presentation allows identification of patients in need for an ICD.