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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 P = 0.003), pre-existing TR (OR 4.30; 95% CI 2.51–7.38; P 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 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 P P Conclusions Patients with RVD receiving pacemaker suffered from increased TR progression, leading to decreased survival. Graphic abstract

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.To evaluate a novel ICM (BIOMONITOR III) regarding all these aspects.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.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,The study demonstrated fast insertion times, low complication rate, high patient acceptance, and favorable long-term sensing and HM performance of the ICM.

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.

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.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.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).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.

Objectives. Patients with heart failure and reduced left ventricular ejection fraction (HFrEF) are prone to ventricular tachyarrhythmias. We tested whether biomarkers C-terminal Endothelin 1 (CT-ET...

Introduction: Right ventricular (RV) leads of permanent pacemakers (PM) contribute or cause tricuspid regurgitation (TR) in up to 45% of implantations, which is associated with poor outcome. While primary lead-induced TR has its origin in direct interaction of the lead and the valve, secondary lead-induced TR has its origin in RV dilatation (RVD). Hypothesis: We hypothesize differences in lead-induced TR and its associated mortality comparing patients with vs. without RVD. Methods: Patients with first implantation of a cardiac PM with at least one transtricuspid RV-lead between May 2000 and April 2015 were retrospectively included. Echo was performed before and after PM implantation. Results: In total, 990 patients were enrolled (Table 1). Patients with RVD had progression of TR of at least one grade in 50.2%, compared to 35.9% in patients without RVD (p 80 years (HR 2.78, 95%CI 2.14-3.61, p 25mm/m2 (HR 1.37, 95%CI 1.06-1.77, p=0.015). Conclusions: RVD is associated with lead-induced progression of TR, which is associated with decreased survival. Patients with RVD and indication for a PM, leadless pacing could be an alternative. If lead-induced TR occurs, transcatheter tricuspid valve intervention is a possibility, especially in patients with RVD.

Background Currently no data are available whether the implantation of right ventricular (RV) pacemaker (PM) lead worsens preexisting primary or secondary (functional due to RV dilatation, RVD) tricuspid regurgitation (TR). Purpose The aim of the present retrospective analysis was to assess TR after PM implantation with a RV lead. Methods Patients with PM implantation (n=990) were enrolled if they had routine echocardiography including assessment of TR before first implantation and immediately after. RVD and severity of TR were characterized visually. Based on RVD in baseline echocardiography, patients were divided into 2 groups: with primary TR (without preexisting RVD, n=743) or secondary TR (with preexisting RVD, n=243). Results Lead-induced worsening of TR was present in both groups (Table 1). Progression from mild/moderate to severe TR was observed in 6.7% of patients with primary TR, compared to 25.6% of patients with secondary TR (P=0.001). Using an ordinal regression model, the probability to progress to severe TR with primary TR was 14.8% (95% CI 11.0%-19.7%), compared to 41.6% (95% CI 40.3%-42.8%) with secondary TR (P Conclusion Preexisting secondary TR was associated with higher rates of lead-induced progression to severe TR compared to primary TR. Leadless pacing or tricuspid valve clipping post-PM implantation could be an option for patients with preexisting secondary TR and indication for a PM. Table 1. Patient characteristics. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): This study was supported by the European Union's Horizon 2020 Future and Emerging Technologies Programme [Grant number 732170].

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.

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 (p0.715 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.

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

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.

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

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.

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.

Summary 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.

Background— Prophylactic defibrillator implantation is recommended in dilated, nonischemic heart disease and left ventricular ejection fraction of ≤0.30 to 0.35. Noninvasive testing should improve accuracy in decision making of prophylactic defibrillator implantation. Methods and Results— We enrolled 60 patients (median age, 57 years) with dilated cardiomyopathy and left ventricular ejection fraction ≤0.50, and 30 control subjects (median age, 59 years) with left ventricular ejection fraction >0.50. The protocol included an initial assessment, a second assessment after 3 years, and a final follow-up: pharmacological baroreflex testing (baroreceptor reflex sensitivity), short-term spectral analysis of heart rate variability (low frequency/high frequency), and long-term time domain analysis (SD of all normal-to-normal R–R intervals), exercise microvolt T wave alternans, and signal-averaged ECG, and corrected QT-time. The median follow-up was 7 years. End points were cardiac death, resuscitated cardiac arrest, and arrhythmic death. Cardiac death was observed in 21 patients. Resuscitated cardiac arrest and arrhythmic death caused by ventricular tachyarrhythmias ≥240 per minute was observed in 7 and 10 patients, respectively. In the single time point analysis, microvolt T wave alternans, baroreceptor reflex sensitivity, and SD of all normal-to-normal R–R intervals at initial testing added significant information regarding cardiac death. Microvolt T wave alternans added information on resuscitated cardiac arrest or arrhythmic death at multiple time points ( P Conclusions— Noninvasive testing and left ventricular ejection fraction could not reliably identify patients with dilated cardiomyopathy at risk of fatal ventricular tachyarrhythmias. Therefore, the strategy to confine prophylactic implantable cardioverter-defibrillator implantation to patients with dilated cardiomyopathy and severely reduced LV function should be reconsidered.

Aims Ventricular arrhythmias are common after acute myocardial infarction (AMI). Endothelin (ET) is a mediator of microvascular dysfunction and cardiac remodeling with arrhythmogenic potential. The aim of this study was to assess safety and feasibility of selective ET-A receptor blockade in ST-elevation acute coronary syndrome (STE-ACS) within a larger randomized trial. Main methods Patients with posterior-wall STE-ACS were randomly assigned to receive intravenous BQ-123 at 400 nmol/min or placebo over 60 min, starting immediately prior to primary percutaneous coronary intervention. Twenty-four hour Holter recordings were performed during hospitalization for STE-ACS and after 6–8 weeks. The predefined primary endpoint was the documentation of ventricular tachycardia and/or late potentials at follow-up. Key findings There was no significant difference in the predefined primary endpoint at 45 (33–62) days (0/16 (0%) in BQ-123 treated patients vs. 1/14 (7%) in the placebo group, p = 0.465). At 2 (1–3) days, an increase in the total number of supraventricular extrasystoles (SVES)/24 h in patients randomized to BQ-123 (45 (17–165) beats vs. 11 (5–72) beats in placebo treated patients, p = 0.025) occurred. This increase was also observed at 45 days (105 (37–216) beats vs. 11 (3–98) beats in placebo treated patients, p = 0.037). There was no significant difference regarding other rhythmologic secondary endpoints between the two groups. Significance Based on the analysis of long-term ECG data, short-term administration of BQ-123 after AMI was safe. Because of the small sample size, no firm conclusion regarding antiarrhythmic efficacy can be drawn.

Background The aim of the study was to investigate the safety and efficacy of a single, remote-magnetic catheter navigation system (MNS) for pulmonary vein isolation (PVI). Methods A total of 107 PVI procedures in 71 patients with paroxysmal (32%), persistent (38%) and longstanding-persistent (30%) atrial fibrillation (AF) were analyzed. A wide area circumferential radiofrequency ablation PVI was performed with either an 8mm MNS (first 35 procedures) or an irrigated MNS (last 36 procedures) catheter. Electrical isolation was confirmed with circular pacing/sensing using the MNS catheter and a coronary sinus catheter. Our follow-up strategy in the first year and upon symptoms thereafter was: clinical check plus 12-lead ECG (100%) and 24h-ECG recordings (76%) at 3month intervals, trans-telephonic ECG (79%) twice daily and upon symptoms (4weeks every 3months), or ECG monitoring via implanted devices (9%). Results The mean procedure time at 1st PVI was 247±61min, and mean fluoroscopy time was 44±18min. The overall complication rate was 2%. Success rates did not differ at the 1st PVI regarding catheter type ( p =0.931) but were dependent on history of AF: patients with paroxysmal AF had the highest success rates of 58% and 29% after 1 and 3years of follow-up, respectively ( p =0.0084). Conclusion PVI with a single MNS catheter is safe and is associated with short fluoroscopy exposition. Despite a rigorous follow-up strategy success rates favorably compare with recently published data on hand-held PVI. Thus, multipolar catheters or a 2nd trans-septal puncture may not be mandatory.

Background Many patients requiring a pacemaker have persistent hypertension with systolic blood pressures above recommended levels. We evaluated a pacemaker‐based Programmable Hypertension Control ( PHC ) therapy that uses a sequence of variably timed shorter and longer atrioventricular intervals. Methods and Results Patients indicated for dual‐chamber pacing with office systolic blood pressure ( oSBP ) >150 mm Hg despite stable medical therapy were implanted with a Moderato™ pulse generator that delivers PHC therapy. Patients were followed for 1 month (Run‐In period) with conventional pacing; those with persistent oSBP >140 mm Hg were included in the study and had PHC therapy activated. The co‐primary efficacy end points were changes in 24‐hour ambulatory systolic blood pressure and oSBP between baseline and 3 months. Safety was assessed by tracking adverse events. Thirty‐five patients met the initial inclusion criteria and underwent Moderato implantation. At 1 month, oSBP was PHC was activated in the remaining 27 patients with baseline office blood pressure 166±11/80±10 mm Hg despite an average of 3.2 antihypertensive medications. During the Run‐In period, oSBP and 24‐hour ambulatory systolic blood pressure decreased by 8±13 and 5±12 mm Hg ( P PHC activation measurements, oSBP decreased by another 16±15 mm Hg and 24‐hour ambulatory systolic blood pressure decreased by an additional 10±13 mm Hg (both P Conclusions In pacemaker patients with persistent hypertension despite medical therapy, oSBP and 24‐hour ambulatory systolic blood pressure are decreased by PHC therapy. Initial indications are that this therapy is a safe and promising therapy for such patients. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02282033.

Background Brugada syndrome (BS) is associated with an increased risk of sudden cardiac death (SCD) caused by ventricular tachyarrhythmia. Thus, implantable cardioverter defibrillators (ICD) became the main therapeutic option in these patients. We aimed to investigate the prevalence of BS in the Eastern Alps as well as the benefit of ICD therapy in this collective. Methods During physical examination before military service, 47,606 Austrian men were screened for Brugada ECG pattern. Furthermore, we followed 4491 patients with arrhythmia during the last two decades, of which 26 patients (20 male; age at diagnosis: 43.2±11.6 years) revealed BS. Diagnosis was based on characteristic ECG either at rest (11 patients) or after provocation with Ajmaline (15 patients). Results The nationwide screening revealed one individual with Brugada ECG (prevalence of 2.10/100,000 inhabitants). Prior to diagnosis of BS, syncope and SCD survival were observed in 7 and 4 patients, respectively; the remaining 15 patients were asymptomatic. ICD were implanted in 17 patients (15 male). Three asymptomatic patients received no ICD because no tachyarrhythmia was inducible on programmed stimulation. Six asymptomatic patients without family history of sudden death refused further evaluation. Mean ICD follow-up period was 57.0±32.2 months. Two patients (11.7%) needed defibrillation therapy. Four patients (23.5%) received exclusively inappropriate shocks (three due to T-wave oversensing, one due to atrial fibrillation). Conclusions Brugada syndrome has a low prevalence in the Eastern alpine region. Patients with BS benefit from ICD implantation, but less frequently than anticipated. The problem of inappropriate ICD discharges is still of major concern.

BACKGROUND AND OBJECTIVE Cardiopulmonary bypass is associated with temperature pertubations that influence extubation time. Common extubation criteria demand a minimum value of core temperature only. The aim of this prospective study was to test the hypothesis that changes in core and skin surface temperature are related to extubation time in patients following normothermic and hypothermic cardiopulmonary bypass. METHODS Forty patients undergoing cardiac surgery were studied; 28 patients had normothermic cardiopulmonary bypass (nasopharyngeal temperature >35.5 degrees C) and 12 had hypothermic cardiopulmonary bypass (28-34 degrees C). In the intensive care unit, urinary bladder temperature and skin surface temperature gradient (forearm temperature minus fingertip temperature: >0 degrees C = vasoconstriction, < or =0 degrees C = vasodilatation) were measured at 30-min intervals for 10 h postoperatively. At the same intervals, the patients were evaluated for extubation according to common extubation criteria. RESULTS On arrival in the intensive care unit the mean urinary bladder temperature was 36.8 +/- 0.5 degrees C in the normothermic group and 36.4+/-0.3 degrees C in the hypothermic group (P = 0.014). The skin surface temperature gradient indicated severe vasoconstriction in the both groups. The shift from vasoconstriction to vasodilatation was faster in normothermic cardiopulmonary bypass patients (138+/-65 min) than in patients after hypothermic cardiopulmonary bypass (186+/-61 min, P = 0.034). There was a linear relation between the time to reach a skin surface temperature gradient = 0 degrees C and extubation time (r2 = 0.56, normothermic group; r2 = 0.82, hypothermic group). CONCLUSIONS The transition from peripheral vasoconstriction to vasodilatation is related to extubation time in patients following cardiac surgery under normothermic as well as hypothermic cardiopulmonary bypass.

We describe a patient with a history of neurocardiogenic syncopes who had a positive headup tilt test that resulted in an lasting asystole lasting 34 seconds. However, the previously carried out Schellong test with a 30-min phase of standing showed a normal result. The patient showed typical orthostatic symptoms while tilted at the angle of 75 degrees. Shortly before asystole occurred, heart rate variability showed high frequency bands, indicating vagal stimulation. The pathophysiology of neurocardiogenic syncope (NCS) in context with heart rate variability is discussed. This patient was successfully treated with propranolol. This case shows the utility of a provocative head-up tilt test in establishing the diagnosis of NCS. If the Schellong test is normal, still further examination by tilt-table test is indispensable.

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.

Pulmonary vein isolation (PVI) for paroxysmal or non-paroxysmal atrial fibrillation (AF) should increase health-related quality of life (QOL). Retrospective cohort study of consecutive patients scheduled for PVI. University Medical Center. QOL was assessed using the physical (PCS) and mental (MCS) component summary scores from the SF-12v2 in patients undergoing PVI (mean 50, range 0–100, with higher scores indicating greater QOL). SF-12v2 was obtained at initial presentation (3-months) before PVI and after PVI at the end of follow-up (mean 1.7 ± 1.4 years) which included: (1) Clinical status, ECG, and 24-h ECG every 3 months, (2) trans-telephonic ECGs for 4 weeks every 3 months, or (3) continuous ECG via implanted devices. A recurrence was any atrial arrhythmia >30 s. Out of 229 patients (73 % males; 58 ± 11 years), 72 % returned SF-12v2 regarding 187 PVI procedures: 56 % for 1st PVI, 48 % for 2nd PVI, 71 % for 3rd PVI, and 44 % for 4th PVI. The mean difference between before and after PVI was 10 for PCS and 9 for MCS. History of paroxysmal or non-paroxysmal AF did not influence QOL (p = 0.724). Patients with an estimated PCS improvement ≥10 or an estimated MCS improvement ≥9 had the best outcome after repeated PVI. Success rates were 72 or 82 % after 1 year compared to 20 and 22 % in patients not achieving this improvement, respectively (p

Background . Cerebral embolization is a major cause of central nervous dysfunction after cardiopulmonary bypass. Experimental studies demonstrate that reductions in arterial carbon dioxide tension (PaCO 2 ) can reduce cerebral embolization during cardiopulmonary bypass. This study examined the effects of brief PaCO 2 manipulations on cerebral embolization in patients undergoing cardiac valve procedures. Methods . Patients were prospectively randomized to either hypocapnia (PaCO 2 = 30 to 32 mm Hg, n=30) or normocapnia (PaCO 2 = 40 to 42 mm Hg, n=31) before aortic cross-clamp removal. With removal of the aortic cross-clamp embolic signals were recorded by transcranial Doppler ultrasonography for the next 15 minutes. Results . Despite significant differences in PaCO 2 , groups did not differ statistically in total cerebral emboli counts. The mean number of embolic events was 107 ± 100 (median, 80) in the hypocapnic group and 135 ± 115 (median, 96) in the normocapnic group, respectively ( p = 0.315). Conclusions . Due to the high between-patient variability in embolization, reductions in PaCO 2 did not result in a statistically significant decrease in cerebral emboli. In contrast to experimental studies, the beneficial effect of hypocapnia on cerebral embolization could not be demonstrated in humans.

Nitric oxide (NO) has been implicated in various aspects of physiological regulation in the gastrointestinal tract. Hence, measurement of luminal NO concentrations is of interest for studying physiological and pathophysiological alterations in NO generation; however, at present, no reliable measurement techniques are available. Here we describe novel approaches for measurement of NO concentrations directly in the gas phase of the stomach and colon in healthy subjects and patients. Studies were conducted in young healthy volunteers (n = 13), intensive care patients (n = 8) and patients undergoing gastroscopy (n = 8) or colonoscopy (n = 8). NO concentrations were measured by chemolumininescence detection in air obtained through a nasogastric tube, after inflation into the stomach of a defined volume of air, or directly in the air suctioned from the endoscope. The mean NO concentration obtained from the stomach of healthy volunteers studied under baseline conditions was 18.0 +/- 2.8 (SEM) p.p.m. Day-to-day reproducibility of NO measurements was high. Tube feeding with a nitrite- and nitrate-free feeding solution left gastric NO concentrations unchanged, but standardized bicycle exercise caused an approximately 30% decrease in NO levels. NO concentrations in intensive care patients were approximately 2 log cycles lower than in healthy volunteers. NO levels in the colon were similar to those in the stomach. We have described two readily applicable techniques for direct, uncontaminated measurement of NO concentrations in the lumen of the gastrointestinal tract. Our finding of a striking reduction in gastric NO concentrations in intensive care patients requires further study.

Anti-tachycardia pacing (ATP) and shock delivery may induce or accelerate tachyarrhythmias in patients with implantable cardioverter-defibrillator (ICD). We investigated the incidence, triggers and impact on mortality of accelerated ventricular tachyarrhythmias.Database analysis concerning ventricular tachyarrhythmias accelerated by ATP or shock in 1275 ICD patients (age at implantation 59.7 ± 14.0 years; 81% male).Within a mean follow-up period of 5.3 ± 4.0 years, intracardiac electrograms were available in 1170 patients (91.8%). Overall 157 episodes of accelerated ventricular tachyarrhythmias were found in 100 of 1170 patients (8.5%). Termination of tachyarrhythmias was achieved by shock delivery in 153 episodes (96.8%). Triggers of accelerated tachyarrhythmias were appropriate ATP in 139 (88.5%) and inappropriate ATP in 14 (8.9%), as well as appropriate and inappropriate shocks in 2 (1.3%) episodes, respectively. Chronic heart failure was significantly correlated with the occurrence and recurrence of acceleration (p0.001). Patients with accelerated ventricular tachyarrhythmia and subsequent shock therapy revealed higher all-cause mortality (HR 1.760; 95% CI 1.286-2.410; p0.001) as well as higher cardiac mortality (HR 2.555; 95% CI 1.446-4.513; p=0.001). The correlation between acceleration and all-cause mortality was independent of left ventricular function (HR 2.076; 95% CI 1.633-2.639; p0.001).Ventricular ATP with arrhythmia acceleration and subsequent shock delivery is a frequent and serious complication of ICD therapy that predominantly occurs in patients with reduced left ventricular function. Finally, occurrence of accelerated ventricular tachyarrhythmias was associated with increased all-cause mortality.

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 VTablation (non-ICD group, n=18). Thirteen patients had an abnormal signal averaged ECG. During 6.5 T2.4 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. D 2005 Elsevier Ireland Ltd. All rights reserved.

To investigate the relationship between changes in core and skin surface temperature and extubation time in patients following normothermic cardiopulmonary bypass (CPB).Prospective observational study.Intensive care unit (ICU) of a university hospital.Patients admitted to the ICU after cardiac surgery.None.Thirty-two patients undergoing cardiac surgery with the use of normothermic CPB were studied. In the ICU, urinary bladder temperature and skin surface temperature gradient (forearm temperature minus fingertip temperature) were measured at 30-min intervals for 10 h postoperatively. Every half-hour an anaesthesiologist, blinded to temperature measurements, checked the possibility of extubation. On arrival in the ICU the mean skin surface temperature gradient of the patients was 1.9+/-1.6 degrees C, indicating vasoconstriction of the dermal vessels (0 degrees C = vasoconstriction,0 degrees C = vasodilation) while the mean urinary bladder temperature was 36.8+/-0.4 degrees C. The change from thermoregulatory vasoconstriction to vasodilation (skin surface temperature gradient of 0 degrees C) was 137+/-49 min after arrival in the ICU. The mean time until extubation was 135+/-55 min after arrival in the ICU. There was a linear relation between a temperature gradient of 0 degrees C and extubation time, r(2)=0.49. Later, 181+/-67 min after arrival in the ICU, the urinary bladder temperature reached its maximum of 38.2+/-0.6 degrees C.This study demonstrates that the transition period from peripheral vasoconstriction to vasodilation provides an opportunity for postoperative extubation.

To evaluate electrophysiologically guided implantable cardioverter defibrillator (ICD) therapy in patients with syncope, structural heart disease and no documented sustained ventricular tachycardia (sVT).Programmed ventricular stimulation (PVS) was performed in 52 patients (age 62+/-10 years): 40 patients had ischaemic and 12 patients had idiopathic dilated cardiomyopathy. On PVS sVT and ventricular fibrillation were induced in seven and four patients, respectively, and two patients spontaneously experienced symptomatic sVT. These patients received an ICD (ICD group, n=13). Non-inducible patients were left on conventional therapy (non-ICD group, n=39). During 5+/-2.8 years five ICD patients received therapies, all appropriate. There were seven non-sudden deaths and overall survival analysis revealed no significant difference. Recurrent syncope occurred in five ICD and four non-ICD patients and did not correlate well with sVT. The positive and negative predictive values of PVS for tachyarrhythmias or sudden death were 36 and 98%, respectively.Syncope per se does not necessarily herald a bad prognosis. PVS identifies high-risk patients. Induction of ventricular fibrillation with double or triple extrastimuli is of limited value. Patients with poor left ventricular function and bad clinical condition benefit most from an ICD. Syncope and sVT are not necessarily correlated during follow-up, which may merit consideration.

Neuromuscular electrical stimulation (NMES) is a frequently applied therapy for the treatment of pain and a therapeutic option to increase thigh muscle strength and endurance capacity in patients with heart failure. Electromagnetic interference (EMI) by the signals with sensing of ICDs is possible. Eight patients with subpectoral ICD systems and different transvenous bipolar sensing leads were subjected to electrical stimulation of the neck and shoulder and of the thighs using different stimulation algorithms. EMI with ventricular sensing was detectable in three of eight subjects. EMI occurred during stimulation of the neck (n = 2) and thigh (n = 2). EMI by NMES with atrial sensing was seen in two of four subjects with dual chamber ICDs. The safety of peripheral NMES has to be individually tested as EMI can also occur in ICD patients with bipolar sensing.

Objectives: To test the hypothesis whether in patients undergoing liver transplantation the antioxidant tirilazad mesylate can reduce hepatic ischaemia-reperfusion injury and improve postoperative outcome. Design: Prospective, randomised, placebo controlled trial. Setting: University hospital. Patients: 20 patients were randomised to receive either tirilazad mesylate or placebo (saline). Interventions: Patients in the tirilazad group (n = 10) received four intravenous infusions of tirilazad at 6-h intervals (men 3 mg/kg, women 3.75 mg/kg) after the induction of anaesthesia. The other patients (n = 10) served as controls. Measurements and results: Plasma levels of malonaldehyde (MDA) were determined after the induction of anaesthesia prior to the infusion of tirilazad (baseline), during the anhepatic period, and 5 min and 24 h after reperfusion. Postoperatively, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and serum cholinesterase were determined daily for 1 week. Compared to baseline, plasma MDA levels did not significantly change during the anhepatic period and after reperfusion and they did not differ between groups. Postoperative liver enzymes and prothrombin time did not differ between groups, but on the first (p = 0.03) and second (p = 0.01) postoperative day cholinesterase levels were significantly higher in tirilazad-treated patients than in control patients. For neither length of stay in the intensive care unit nor hospital stay were any differences observed between groups. Conclusions: In patients undergoing liver transplantation, tirilazad does not improve overall outcome. Whether the higher cholinesterase levels on the first 2 postoperative days in tirilazad treated patients indicates an earlier recovery of liver function remains to be tested.

Background: Anti-tachycardia pacing (ATP) and shock delivery may induce or accelerate tachyarrhythmias in patients with implantable cardioverter defibrillator (ICD). Methods: We investigated the triggers and the clinical outcome of ventricular tachyarrhythmias accelerated by ATP or shock. Results: ICD were implanted in 1275 patients (age at implantation 59.7±14.0 years). Within a mean follow-up of 5.3±4.0 years, intracardiac electrograms were available in 1170 patients (91.8%). Overall 157 episodes of accelerated ventricular tachyarrhythmias were found in 100 of 1170 patients (8.5%). Termination of tachyarrhythmias was achieved by shock delivery in 153 episodes (96.8%). Triggers of accelerated tachyarrhythmias were appropriate ATP in 139 (88.5%) and inappropriate ATP in 14 (8.9%), as well as appropriate and inappropriate shocks in 2 (1.3%) episodes, respectively. Patients with accelerated ventricular tachyarrhythmia and shock therapy revealed higher all-cause mortality (47% versus 29.9%; p