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OBJECTIVES: The optimal targeted temperature in patients with shockable rhythm is unclear, and current guidelines recommend targeted temperature management with a correspondingly wide range between 32°C and 36°C. Our aim was to study survival and neurologic outcome associated with targeted temperature management strategy in postarrest patients with initial shockable rhythm.DESIGN: Observational substudy of the Coronary Angiography after Cardiac Arrest without ST-segment Elevation trial.SETTING: Nineteen hospitals in The Netherlands.PATIENTS: The Coronary Angiography after Cardiac Arrest trial randomized successfully resuscitated patients with shockable rhythm and absence of ST-segment elevation to a strategy of immediate or delayed coronary angiography. In this substudy, 459 patients treated with mild therapeutic hypothermia (32.0-34.0°C) or targeted normothermia (36.0-37.0°C) were included. Allocation to targeted temperature management strategy was at the discretion of the physician.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: After 90 days, 171 patients (63.6%) in the mild therapeutic hypothermia group and 129 (67.9%) in the targeted normothermia group were alive (hazard ratio, 0.86 [95% CI, 0.62-1.18]; log-rank p = 0.35; adjusted odds ratio, 0.89; 95% CI, 0.45-1.72). Patients in the mild therapeutic hypothermia group had longer ICU stay (4 d [3-7 d] vs 3 d [2-5 d]; ratio of geometric means, 1.32; 95% CI, 1.15-1.51), lower blood pressures, higher lactate levels, and increased need for inotropic support. Cerebral Performance Category scores at ICU discharge and 90-day follow-up and patient-reported Mental and Physical Health Scores at 1 year were similar in the two groups.CONCLUSIONS: In the context of out-of-hospital cardiac arrest with shockable rhythm and no ST-elevation, treatment with mild therapeutic hypothermia was not associated with improved 90-day survival compared with targeted normothermia. Neurologic outcomes at 90 days as well as patient-reported Mental and Physical Health Scores at 1 year did not differ between the groups.

Contains fulltext : 235070.pdf (Publisher’s version ) (Open Access) BACKGROUND: The effect of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients who are successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) on left ventricular function is currently unknown. METHODS: This prespecified sub-study of a multicentre trial evaluated 552 patients, successfully resuscitated from out-of-hospital cardiac arrest without signs of STEMI. Patients were randomized to either undergo immediate coronary angiography or delayed coronary angiography, after neurologic recovery. All patients underwent PCI if indicated. The main outcomes of this analysis were left ventricular ejection fraction and end-diastolic and systolic volumes assessed by cardiac magnetic resonance imaging or echocardiography. RESULTS: Data on left ventricular function was available for 397 patients. The mean (± standard deviation) left ventricular ejection fraction was 45.2% (±12.8) in the immediate angiography group and 48.4% (±13.2) in the delayed angiography group (mean difference: -3.19; 95% confidence interval [CI], -6.75 to 0.37). Median left ventricular end-diastolic volume was 177 ml in the immediate angiography group compared to 169 ml in the delayed angiography group (ratio of geometric means: 1.06; 95% CI, 0.95-1.19). In addition, mean left ventricular end-systolic volume was 90 ml in the immediate angiography group compared to 78 ml in the delayed angiography group (ratio of geometric means: 1.13; 95% CI 0.97-1.32). CONCLUSION: In patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, immediate coronary angiography was not found to improve left ventricular dimensions or function compared with a delayed angiography strategy. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register number, NTR4973.

Contains fulltext : 229274.pdf (Publisher’s version ) (Closed access) BACKGROUND: Whether sex is associated with outcomes of out-of-hospital cardiac arrest (OHCA) is unclear. OBJECTIVES: This study examined sex differences in survival in patients with OHCA without ST-segment elevation myocardial infarction (STEMI). METHODS: Using data from the randomized controlled Coronary Angiography after Cardiac Arrest (COACT) trial, the primary point of interest was sex differences in OHCA-related one-year survival. Secondary points of interest included the benefit of immediate coronary angiography compared to delayed angiography until after neurologic recovery, angiographic and clinical outcomes. RESULTS: In total, 522 patients (79.1% men) were included. Overall one-year survival was 59.6% in women and 63.4% in men (HR 1.18; 95% CI: 0.76-1.81;p = 0.47). No cardiovascular risk factors were found that modified survival. Women less often had significant coronary artery disease (CAD) (37.0% vs. 71.3%;p

IMPORTANCE: Ischemic heart disease is a common cause of cardiac arrest. However, randomized data on long-term clinical outcomes of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients successfully resuscitated from cardiac arrest in the absence of ST segment elevation myocardial infarction (STEMI) are lacking. OBJECTIVE: To determine whether immediate coronary angiography improves clinical outcomes at 1 year in patients after cardiac arrest without signs of STEMI, compared with a delayed coronary angiography strategy. DESIGN, SETTING, AND PARTICIPANTS: A prespecified analysis of a multicenter, open-label, randomized clinical trial evaluated 552 patients who were enrolled in 19 Dutch centers between January 8, 2015, and July 17, 2018. The study included patients who experienced out-of-hospital cardiac arrest with a shockable rhythm who were successfully resuscitated without signs of STEMI. Follow-up was performed at 1 year. Data were analyzed, using the intention-to-treat principle, between August 29 and October 10, 2019. INTERVENTIONS: Immediate coronary angiography and PCI if indicated or coronary angiography and PCI if indicated, delayed until after neurologic recovery. MAIN OUTCOMES AND MEASURES: Survival, myocardial infarction, revascularization, implantable cardiac defibrillator shock, quality of life, hospitalization for heart failure, and the composite of death or myocardial infarction or revascularization after 1 year. RESULTS: At 1 year, data on 522 of 552 patients (94.6%) were available for analysis. Of these patients, 413 were men (79.1%); mean (SD) age was 65.4 (12.3) years. A total of 162 of 264 patients (61.4%) in the immediate angiography group and 165 of 258 patients (64.0%) in the delayed angiography group were alive (odds ratio, 0.90; 95% CI, 0.63-1.28). The composite end point of death, myocardial infarction, or repeated revascularization since the index hospitalization was met in 112 patients (42.9%) in the immediate group and 104 patients (40.6%) in the delayed group (odds ratio, 1.10; 95% CI, 0.77-1.56). No significant differences between the groups were observed for the other outcomes at 1-year follow-up. For example, the rate of ICD shocks was 20.4% in the immediate group and 16.2% in the delayed group (odds ratio, 1.32; 95% CI, 0.66-2.64). CONCLUSIONS AND RELEVANCE: In this trial of patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, a strategy of immediate angiography was not found to be superior to a strategy of delayed angiography with respect to clinical outcomes at 1 year. Coronary angiography in this patient group can therefore be delayed until after neurologic recovery without affecting outcomes. TRIAL REGISTRATION: trialregister.nl Identifier: NTR4973

Sex differences in out-of-hospital cardiac arrest (OHCA) patients are increasingly recognized. Although it has been found that post-resuscitated women are less likely to have significant coronary artery disease (CAD) than men, data on follow-up in these patients are limited. Data for this data in brief article was obtained as a part of the randomized controlled Coronary Angiography after Cardiac Arrest without ST-segment elevation (COACT) trial. The data supplements the manuscript "Sex differences in out-of-hospital cardiac arrest patients without ST-segment elevation: A COACT trial substudy" were it was found that women were less likely to have significant CAD including chronic total occlusions, and had worse survival when CAD was present. The dataset presented in this paper describes sex differences on interventions, implantable-cardioverter defibrillator (ICD) shocks and hospitalizations due to heart failure during one-year follow-up in patients successfully resuscitated after OHCA. Data was derived through a telephone interview at one year with the patient or general practitioner. Patients in this randomized dataset reflects a homogenous study population, which can be valuable to further build on research regarding long-term sex differences and to further improve cardiac care. (C) 2020 The Authors. Published by Elsevier Inc.

Introduction In the care of heart failure patients, telemonitoring is receiving growing attention. The main purpose of this study was to determine the effect of continuous telemonitoring with an implantable loop recorder (ILR, Reveal XT), a novel strategy in the management of stable heart failure patients without a cardiac implantable device. Furthermore, little is known about the incidence of subclinical arrhythmias in this specific group of patients. Materials and Methods Stable heart failure patients, New York Heart Association Class II and III, without recent hospitalisation or upcoming intervention, were included. After implantation of the ILR there was regular contact with the research nurse on a pre-specified basis. Clinic visits and telephonic interviews were alternated for a minimum of 1 year. Parallel visits to their treating physician continued according to standard care. The treating physician was blinded for the ILR findings, accept for pre-specified, significant arrhythmic events. Results Thirty patients were included and followed for a median duration of 12 months. In 13 patients, data from the loop recorder led to therapeutic changes. One patient received a pacemaker. Eight patients developed atrial fibrillation, all subclinical, with a mean burden of 65.8 ± 173.2 min/day. Conclusion The use of an ILR could potentially impact patient management. Additional study is needed in different patient populations (e. g. higher risk groups) to assess if an ILR could also impact on endpoints such as heart failure hospitalisation.

In natural situations, speech perception often takes place during the concurrent execution of other cognitive tasks, such as listening while viewing a visual scene. The execution of a dual task typically has detrimental effects on concurrent speech perception, but how exactly cognitive load disrupts speech encoding is still unclear. The detrimental effect on speech representations may consist of either a general reduction in the robustness of processing of the speech signal (‘noisy encoding’), or, alternatively it may specifically influence the temporal sampling of the sensory input, with listeners missing temporal pulses, thus underestimating segmental durations (‘shrinking of time’). The present study investigated whether and how spectral and temporal cues in a precursor sentence that has been processed under high vs. low cognitive load influence the perception of a subsequent target word. If cognitive load effects are implemented through ‘noisy encoding’, increasing cognitive load during the precursor should attenuate the encoding of both its temporal and spectral cues, and hence reduce the contextual effect that these cues can have on subsequent target sound perception. However, if cognitive load effects are expressed as ‘shrinking of time’, context effects should not be modulated by load, but a main effect would be expected on the perceived duration of the speech signal. Results from two experiments indicate that increasing cognitive load (manipulated through a secondary visual search task) did not modulate temporal (Experiment 1) or spectral context effects (Experiment 2). However, a consistent main effect of cognitive load was found: increasing cognitive load during the precursor induced a perceptual increase in its perceived speech rate, biasing the perception of a following target word towards longer durations. This finding suggests that cognitive load effects in speech perception are implemented via ‘shrinking of time’, in line with a temporal sampling framework. In addition, we argue that our results align with a model in which early (spectral and temporal) normalization is unaffected by attention but later adjustments may be attention-dependent.

PiNCeR is a corpus of speech recordings from Dutch speakers who named pictures at different speaking rates. Participants named pre-familiarised ˈ(C)CV.CVC words (e.g., snavel [ˈsnaː.vəl] “beak”) from line drawings displayed in groups of 8 arranged on a ‘clock face’. A cursor moved clockwise from picture to picture to indicate at which of three trained rates (fast, medium and slow) participants were required to name the pictures. Annotation was performed using the POnSS tool (Rodd, Decuyper, & ten Bosch, 2019), where manual and automatic segmentation is combined to yield accurate word onsets and offsets. To detect the onset and offset times of syllables within words, we identified excursions of above-average acoustic instability between the vowel of the initial syllable and the first consonant of the second syllable (Rodd, Bosker, ten Bosch, & Ernestus, 2019). This approach was licensed by careful control of segmental content in the target words to maximise correspondence between acoustics and articulation. The PiNCeR corpus was intended for use in modelling control of speaking rate (Rodd, Bosker, Ernestus, et al., 2019), but may be of interest for other purposes. Trial-level recordings from two related experiments are made available for 25 participants (12 for Experiment 1, 13 for Experiment 2), along with the onset and offset times of the words and the syllables.

Background Ischemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography and percutaneous coronary intervention (PCI) in the treatment of patients who have been successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains uncertain. Methods In this multicenter trial, we randomly assigned 552 patients who had cardiac arrest without signs of STEMI to undergo immediate coronary angiography or coronary angiography that was delayed until after neurologic recovery. All patients underwent PCI if indicated. The primary end point was survival at 90 days. Secondary end points included survival at 90 days with good cerebral performance or mild or moderate disability, myocardial injury, duration of catecholamine support, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, major bleeding, occurrence of acute kidney injury, need for renal-replacement therapy, time to target temperature, and neurologic status at discharge from the intensive care unit. Results At 90 days, 176 of 273 patients (64.5%) in the immediate angiography group and 178 of 265 patients (67.2%) in the delayed angiography group were alive (odds ratio, 0.89; 95% confidence interval [CI], 0.62 to 1.27; P=0.51). The median time to target temperature was 5.4 hours in the immediate angiography group and 4.7 hours in the delayed angiography group (ratio of geometric means, 1.19; 95% CI, 1.04 to 1.36). No significant differences between the groups were found in the remaining secondary end points. Conclusions Among patients who had been successfully resuscitated after out-of-hospital cardiac arrest and had no signs of STEMI, a strategy of immediate angiography was not found to be better than a strategy of delayed angiography with respect to overall survival at 90 days. (Funded by the Netherlands Heart Institute and others; COACT Netherlands Trial Register number, .)Patients who had cardiac arrest without ST-segment elevation were assigned to undergo either immediate coronary angiography or delayed coronary angiography (after neurologic recovery). All patients underwent PCI if indicated. There was no significant between-group difference in overall survival at 90 days.

Background Ischemic heart disease is a major cause of out-of-hospital cardiac arrest. The role of immediate coronary angiography (CAG) and percutaneous coronary intervention (PCI) after restoration of spontaneous circulation following cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) remains debated.Hypothesis We hypothesize that immediate CAG and PCI, if indicated, will improve 90-day survival in post cardiac arrest patients without signs of STEMI.Design In a prospective, multicenter, randomized controlled clinical trial, 552 post cardiac arrest patients with restoration of spontaneous circulation and without signs of STEMI will be randomized in a 1:1 fashion to immediate CAG and PCI (within 2 hours) versus initial deferral with CAG and PCI after neurological recovery. The primary end point of the study is 90-day survival. The secondary end points will include 90-day survival with good cerebral performance or minor/moderate disability, myocardial injury, duration of inotropic support, occurrence of acute kidney injury, need for renal replacement therapy, time to targeted temperature control, neurological status at intensive care unit discharge, markers of shock, recurrence of ventricular tachycardia, duration of mechanical ventilation, and reasons for discontinuation of treatment.Summary The COACT trial is a multicenter, randomized, controlled clinical study that will evaluate the effect of an immediate invasive coronary strategy in post cardiac arrest patients without STEMI on 90-day survival.

Speech is an acoustic signal with inherent amplitude modulations in the 1-9 Hz range. Recent models of speech perception propose that this rhythmic nature of speech is central to speech recognition. Moreover, rhythmic amplitude modulations have been shown to have beneficial effects on language processing and the subjective impression listeners have of the speaker. This study investigated the role of amplitude modulations in the political arena by comparing the speech produced by Hillary Clinton and Donald Trump in the three presidential debates of 2016. Inspection of the modulation spectra, revealing the spectral content of the two speakers’ amplitude envelopes after matching for overall intensity, showed considerably greater power in Clinton’s modulation spectra (compared to Trump’s) across the three debates, particularly in the 1-9 Hz range. The findings suggest that Clinton’s speech had a more pronounced temporal envelope with rhythmic amplitude modulations below 9 Hz, with a preference for modulations around 3 Hz. This may be taken as evidence for a more structured temporal organization of syllables in Clinton’s speech, potentially due to more frequent use of preplanned utterances. Outcomes are interpreted in light of the potential beneficial effects of a rhythmic temporal envelope on intelligibility and speaker perception.

Aims Adult congenital heart disease (ACHD) predisposes to infective endocarditis (IE). Surgical advancements have changed the ACHD population, whereas associated prosthetic material may constitute additional IE targets. We aimed to prospectively determine contemporary incidence, risk factors, and predictors of IE in a nationwide ACHD cohort, focusing on the presence of prosthetics. Methods and results We identified 14 224 patients prospectively followed in the CONCOR ACHD registry (50.5% female, median age 33.6years). IE incidence was determined using Poisson regression, risk factors and predictors using Cox regression. Overall incidence was 1.33 cases/1000 person-years (124 cases in 93 562 person-years). For risk-factor analysis, presence of prosthetics was forced—as separate time-updated variables for specific prosthetics—into a model with baseline characteristics univariably associated with IE. Valve-containing prosthetics were independently associated with greater risk both short- and long term after implantation [0–6 months: hazard ratio (HR) = 17.29; 7.34–40.70, 6–12 months: HR = 15.91; 6.76–37.45, beyond 12 months: HR = 5.26; 3.52–7.86], non-valve-containing prosthetics, including valve repair, only in the first 6 months after implantation (HR = 3.34; 1.33–8.41), not thereafter. A prediction model was derived and validated using bootstrapping techniques. Independent predictors of IE were baseline valve-containing prosthetics, main congenital heart defect, multiple defects, previous IE, and sex. The model had fair discriminative ability and provided accurate predictions up to 10 years. Conclusions This study provides IE incidence estimates, and determinants of IE risk in a nationwide ACHD cohort. Our findings, essentially informing IE prevention guidelines, indicate valve-containing prosthetics as a main determinant of IE risk whereas other prosthetics, including valve-repair, are not associated with increased risk long term after implantation.

The oral fluency level of an L2 speaker is often used as a measure in assessing language proficiency. The present study reports on four experiments investigating the contributions of three fluency aspects (pauses, speed and repairs) to perceived fluency. In Experiment 1 untrained raters evaluated the oral fluency of L2 Dutch speakers. Using specific acoustic measures of pause, speed and repair phenomena, linear regression analyses revealed that pause and speed measures best predicted the subjective fluency ratings, and that repair measures contributed only very little. A second research question sought to account for these results by investigating perceptual sensitivity to acoustic pause, speed and repair phenomena, possibly accounting for the results from Experiment 1. In Experiments 2–4 three new groups of untrained raters rated the same L2 speech materials from Experiment 1 on the use of pauses, speed and repairs. A comparison of the results from perceptual sensitivity (Experiments 2–4) with fluency perception (Experiment 1) showed that perceptual sensitivity alone could not account for the contributions of the three aspects to perceived fluency. We conclude that listeners weigh the importance of the perceived aspects of fluency to come to an overall judgment.

Background— Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome associated with mutations in the cardiac ryanodine receptor gene ( Ryr2 ) in the majority of patients. Previous studies of CPVT patients mainly involved probands, so current insight into disease penetrance, expression, genotype-phenotype correlations, and arrhythmic event rates in relatives carrying the Ryr2 mutation is limited. Methods and Results— One-hundred sixteen relatives carrying the Ryr2 mutation from 15 families who were identified by cascade screening of the Ryr2 mutation causing CPVT in the proband were clinically characterized, including 61 relatives from 1 family. Fifty-four of 108 antiarrhythmic drug-free relatives (50%) had a CPVT phenotype at the first cardiological examination, including 27 (25%) with nonsustained ventricular tachycardia. Relatives carrying a Ryr2 mutation in the C-terminal channel-forming domain showed an increased odds of nonsustained ventricular tachycardia (odds ratio, 4.1; 95% CI, 1.5–11.5; P =0.007, compared with N-terminal domain) compared with N-terminal domain. Sinus bradycardia was observed in 19% of relatives, whereas other supraventricular dysrhythmias were present in 16%. Ninety-eight (most actively treated) relatives (84%) were followed up for a median of 4.7 years (range, 0.3–19.0 years). During follow-up, 2 asymptomatic relatives experienced exercise-induced syncope. One relative was not being treated, whereas the other was noncompliant. None of the 116 relatives died of CPVT during a 6.7-year follow-up (range, 1.4–20.9 years). Conclusions— Relatives carrying an Ryr2 mutation show a marked phenotypic diversity. The vast majority do not have signs of supraventricular disease manifestations. Mutation location may be associated with severity of the phenotype. The arrhythmic event rate during follow-up was low.

Amiodarone effectively suppresses atrial fibrillation but causes many adverse events.To compare major events in patients randomized to receive episodic amiodarone treatment with those who received continuous amiodarone treatment while still aiming to prevent atrial fibrillation.A randomized trial of 209 ambulatory patients with recurrent symptomatic persistent atrial fibrillation, conducted from December 2002 through March 2007 at 7 Dutch medical centers.Patients were randomly assigned to receive either episodic or continuous amiodarone treatment after electrical cardioversion following amiodarone loading. Episodic amiodarone treatment was discontinued after a month of sinus rhythm and reinitiated if atrial fibrillation relapsed (1 month peri-electrical cardioversion). In the continuous treatment group amiodarone was maintained throughout.The primary end point was a composite of amiodarone and underlying heart disease-related major events. The secondary end points were all-cause mortality and cardiovascular hospitalizations.After a median follow-up of 2.1 years (range, 0.4-2.5 years), 51 (48%) of those receiving episodic treatment vs 64 (62%) receiving continuous treatment had sinus rhythm (P = .05). There were 85 atrial fibrillation recurrences (80%) among the episodic treatment group vs 56 (54%) in the continuous treatment group (P.001). No significant difference existed in the incidence of the primary composite end point between each group (37 [35%] episodic vs 34 [33%] continuous; incidence rate difference, 0.2; 95% confidence interval [CI], -10.2 to 10.6). However, there were nonstatistically significant differences in the incidence of amiodarone-related major events (20 [19%] episodic vs 25 [24%] continuous; incidence rate difference, -2.0; 95% CI, -8.7 to 4.6) and underlying heart disease-related major events (17 [16%] episodic vs 9 [9%] continuous; incidence rate difference, 3.6; 95% CI, -1.6 to 8.7). All-cause mortality and cardiovascular hospitalizations were higher among those receiving episodic treatment (56 [53%] vs 35 [34%], P = .02).In this study population, there was no difference in the composite of amiodarone and cardiac major adverse events between groups. However, patients receiving episodic treatment had a significantly increased rate of atrial fibrillation recurrence and a significantly higher rate of all-cause mortality and cardiovascular hospitalizations.clinicaltrials.gov Identifier: NCT00392431.

OBJECTIVES The VERDICT (Verapamil Versus Digoxin and Acute Versus Routine Serial Cardioversion Trial) is a prospective, randomized study to investigate whether: 1) acutely repeated serial electrical cardioversions (ECVs) after a relapse of atrial fibrillation (AF); and 2) prevention of intracellular calcium overload by verapamil, decrease intractability of AF.BACKGROUND Rhythm control is desirable in patients suffering from symptomatic AF.METHODS A total of 144 patients with persistent AF were included. Seventy-four (51%) patients were randomized to the acute (within 24 h) and 70 (49%) patients to the routine serial ECVs, and 74 (51%) patients to verapamil and 70 (49%) patients to digoxin for rate control before ECV and continued during follow-up (2 X 2 factorial design). Class III antiarrhythmic drugs were used after a relapse of AF. Follow-up was 18 months.RESULTS At baseline, there were no significant differences between the groups, except for beta-blocker use in the verapamil versus digoxin group (38% vs. 60%, respectively, p = 0.01). At follow-up, no difference in the occurrence of permanent AF between the acute and the routine cardioversion groups was observed (32% [95% confidence intervals (CI)] 22 to 44) vs. 31% [95% CI 21 to 44], respectively, p = NS), and also no difference between the verapamil- and the digoxin-randomized patients (28% [95% CI 19 to 40] vs. 36% [95% CI 25 to 48] respectively, p = NS). Multivariate Cox regression analysis revealed that lone digoxin use was the only significant predictor of failure of rhythm control treatment (hazard ratio 2.2 [95% CI 1.1 to 4.4], p = 0.02).CONCLUSIONS An acute serial cardioversion strategy does not improve long-term rhythm control in comparison with a routine serial cardioversion strategy. Furthermore, verapamil has no beneficial effect in a serial cardioversion strategy.

BACKGROUND: Recent studies demonstrated that rate control is an acceptable alternative for rhythm control in patients with persistent atrial fibrillation (AF). However, optimal heart rate during AF is still unknown.OBJECTIVE: To show that in patients with permanent AF, lenient rate control is not inferior to strict rate control in terms of cardiovascular mortality, morbidity, neurohormonal activation, New York Heart Association class for heart failure, left ventricular function, left atrial size, quality of life, and costs.METHODS: The RACE II study is a prospective multicenter trial in The Netherlands that will randomize 500 patients with permanent AF (< or = 12 months) to strict or lenient rate control. Strict rate control is defined as a mean resting heart rate < 80 beats per minute (bpm) and heart rate during minor exercise < 110 bpm. After reaching the target, a 24-hour Holter monitoring will be performed. If necessary, drug dose reduction and/or pacemaker implantation will be performed. Lenient rate control is defined as a resting heart rate < 110 bpm. Patients will be seen after 1, 2, and 3 months (for titration of rate control drugs) and yearly thereafter. We anticipate a 25% 2.5-year cardiovascular morbidity and mortality in both groups.RESULTS: Enrollment started in January 2005 in 29 centers in The Netherlands and is expected to be concluded in June 2006. Follow-up will be at least 2 years with a maximum of 3 years.CONCLUSION: This study should provide data how to treat patients with permanent AF.

OBJECTIVES The purpose of this study was to evaluate left ventricular function and atrial and ventricular diameters in patients with persistent atrial fibrillation (AF) treated with rate or rhythm control.BACKGROUND Restoration of sinus rhythm inpatients with persistent AF may improve left ventricular function and reduce atrial dimensions. Adequate rate control in AF may preserve ventricular function.METHODS In 335 patients included in the RAte Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study, echocardiography was performed at baseline and 1- and 2-year follow-up. Echocardiography was compared between patients randomized to rate control (n = 160) and rhythm control (n = 175). In the rhythm control group, echocardiography was compared between patients with AF versus sinus rhythm at study end. Multivariate analysis was performed to determine parameters related to improvement of left ventricular function and increase of atrial diameters.RESULTS Fractional shortening improved significantly under rate and rhythm control (31 - 10% at baseline to 33 +/- 9% at 2 years, and from 30 - 10% to 34 - 9%; both P CONCLUSIONS Routine rate control prevents deterioration of left ventricular function. Maintenance of sinus rhythm is associated with improvement of left ventricular function and reduction of atrial sizes.

Aims To evaluate costs between a rate and rhythm control strategy in persistent atrial. fibrillation.Methods and results In a prospective substudy of RACE (Rate control versus electrical cardioversion for persistent atrial. fibrillation) in 428 of the total 522 patients (206 rate control and 222 rhythm control), a cost-minimisation and cost-effectiveness analysis was performed to assess cost-effectiveness of the treatment strategies.After a mean follow-up of 2.3 +/- 0.6 years, the primary endpoint (cardiovascular morbidity and mortality) occurred in 17.5% (36/202) of the rate control patients and in 21.2% (47/222) of the rhythm control patients. Mean costs per patient under rate control were EURO 7386 and EURO 8284 under rhythm control. Cost-effectiveness analysis showed that per avoided endpoint under rate control, the cost savings were EURO 24944. Under rhythm control, more costs were generated due to electrical cardioversions, hospital admissions and anti-arrhythmic medication. Costs were higher in older patients, patients with underlying heart disease, those who reached a primary endpoint and women. Heart rhythm at the end of study, did not influence costs.Conclusions Rate control is more cost-effective than rhythm control for treatment of persistent atrial. fibrillation. Underlying heart disease but not heart rhythm largely accounts for costs. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.

Aim Differential drug treatment guided by the underlying heart dis- ease may improve outcome of rhythm control therapy. In the present study we investigated in a well-defined group with either lone atrial fibrillation (AF) or hyper- tension whether there were differences in rhythm control outcome between both groups in relation to the use of cardiovascular drugs. Methods and results One hundred sixty-two patients were included after success- ful cardioversion of persistent AF. None of the patients was given a class I or III antiarrhythmic drug. Patients' heart rhythm was checked 3 times a day, using transtelephonic monitoring for 1 month after cardioversion. One month after cardioversion up to 68% of patients had a recurrence of persistent AF. During the first 3 days almost no recurrences were seen on beta-blocker therapy whereas recurren- ces peaked on day 2e3 in the absence of beta-blockers. Univariate analysis showed that the use of beta-adrenergic receptor blockers and the presence of hypertension were associated with a lower recurrence rate at 1 month. Multivariate logistic re- gression analysis demonstrated that beta-blockade was the only statistically signif- icant parameter predicting sinus rhythm at 1 month (OR 0.40, 95% CI 0.19e0.86, P ¼ 0:02). Conclusions Compared with lone AF patients, patients in the setting of hyperten- sion maintain sinus rhythm much better after cardioversion when treated with a beta-blocker. Beta-blockade protects, in particular, against the early subacute re- currences. These findings underscore the importance of a differential approach

Objectives We studied the influence of rate control or rhythm control in patients with persistent atrial fibrillation (AF) on quality of life (QoL). Background Atrial fibrillation may cause symptoms like fatigue and dyspnea. This can impair QoL. Treatment of AF with either rate or rhythm control may influence QoL. Methods Quality of life was assessed in patients included in the Rate Control Versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study (rate vs. rhythm control in persistent AF). Rate control patients (n = 175) were given negative chronotropic drugs and oral anticoagulation. Rhythm control patients (n = 177) received serial electrocardioversion, antiarrhythmic drugs, and oral anticoagulation, as needed. Quality of life was studied using the Short Form (SF)-36 health survey questionnaire at baseline, one year, and the end of the study (after 2 to 3 years of follow-up). At baseline, QoL was compared with that of healthy control subjects. Patient characteristics related to QoL changes were determined. Results Mean follow-up was 2.3 years. At baseline, QoL was lower in patients than in age-matched healthy controls. At study end, under rate control, three subscales of the SF-36 improved. Under rhythm control, no significant changes occurred compared with baseline. At study end, QoL was comparable between both groups. The presence of complaints of AF at baseline, a short duration of AF, and the presence of sinus rhythm (SR) at the end of follow-up, rather than the assigned strategy, were associated with QoL improvement. Conclusions Quality of life is impaired in patients with AF compared with healthy controls. Treatment strategy does not affect QoL. Patients with complaints related to AF, however, may benefit from rhythm control if SR can be maintained.

Introduction: Many relapses of atrial fibrillation (AF) occur, especially during the first week(s) after electrical cardioversion (ECV), The aim of the present study was to compare in a randomized design the efficacy of verapamil (intracellular calcium lowering) versus digoxin (calcium increasing) for maintenance of sinus rhythm after ECV. Methods and Results: Ninety-seven patients with persistent AF were randomized to verapamil (n = 49) or digoxin (n = 48) for 1 month before and 1 month after ECV. The first month after ECV, patients recorded heart rhythm using daily transtelephonic monitoring. No additional antiarrhythmic drugs were given, Of the 97 patients, 43 patients (20 verapamil) underwent ECV per protocol. Median previous AF duration was 18 and 26 days for verapamil and digoxin, respectively. There were no differences in atrial dimensions and underlying heart disease between the two groups. The success rate of ECV was 75% versus 83% (P = NS). After 1 month, 47% versus 53% (P = NS) had recurrence of AF, Median time to recurrence was 5 days (range 0 to 26) versus 8 days (range 2 to 28) (P = NS), respectively. Conclusion: Stand-alone intracellular calcium lowering by verapamil around ECV does not enhance cardioversion outcome.

BACKGROUND: Rate control is often the therapy of choice for atrial fibrillation. Guidelines recommend strict rate control, but this is not based on clinical evidence. We hypothesized that lenient rate control is not inferior to strict rate control for preventing cardiovascular morbidity and mortality in patients with permanent atrial fibrillation. METHODS: We randomly assigned 614 patients with permanent atrial fibrillation to undergo a lenient rate-control strategy (resting heart rate

OBJECTIVE--To assess the accuracy of four enzymatic tests, including early release rates of creatine kinase and alpha-hydroxybutyrate dehydrogenase, in assessing coronary reperfusion after thrombolytic therapy. DESIGN--A prospective clinical trial identifying patients with a successful thrombolytic treatment. PATIENTS--Eighty nine patients with acute myocardial infarction were studied. Arteriography showed a closed infarct related artery in all of them. Reperfusion due to thrombolysis occurred in 74 patients and there was no reperfusion in 15 patients. RESULTS--The 74 patients showing coronary reperfusion had a significantly shorter time to peak creatine kinase activity, higher early release rates for creatine kinase and alpha-hydroxybutyrate dehydrogenase, and a more rapid release of alpha-hydroxybutyrate dehydrogenase (ratio of cumulative release of alpha-hydroxybutyrate dehydrogenase during the first 24 hours to that 72 hours after infarction). All these differences were statistically significant (p less than 0.001). Optimum cut off levels were determined with decision level plots and the accuracy of the four enzymatic tests was calculated. Accuracy was low for all four tests (73%, 70%, 70%, and 82%). CONCLUSION--None of the four enzymatic tests accurately predicted the perfusion state of the infarct related coronary artery after thrombolysis. These tests cannot be used reliably in routine clinical practice as non-angiographic markers of coronary reperfusion.

We report a case of serum-sickness-like illness in a 47-year-old patient who received early high-dose intravenous and intracoronary streptokinase following acute myocardial infarction. The picture comprised severe arthralgias, fever, an urticarial rash and marked elevation of circulating immune complexes. This case represents a rare complication of streptokinase therapy.

Bijzondere vorm van cardiomyopathie met vervanging van normaal rechterventrikelmyocard door vet en fibrotisch weefsel.

OBJECTIVES The purpose of this study was to evaluate the hypothesis that presumed reversion of electrical remodeling after cardioversion of atrial fibrillation (AF) restores the efficacy of flecainide.BACKGROUND Flecainide loses its efficacy to cardiovert when AF has been present for more than 24 hours. Most probably, the loss is caused by atrial electrical remodeling. Studies suggest electrical remodeling is completely reversible within 4 days after restoration of sinus rhythm (SR).METHODS One hundred eighty-one patients with persistent AF (median duration 3 months) were included in this prospective study. After failure of pharmacologic cardioversion by flecainide 2 mg/kg IV (maximum 150 mg in 10 minutes) and subsequent successful electrical cardioversion, we performed intense transtelephonic rhythm monitoring three times daily for 1 month. In case of AF recurrence, a second cardioversion by flecainide was attempted as soon as possible.RESULTS AF recurred in 123 patients (68%). Successful cardioversion by flecainide occurred only when SR had been maintained for more than 4 days (7/51 patients [14%]). Failure to cardiovert was associated with a prolonged duration of the recurrent AF episode and concurrent digoxin use. Multivariate logistic regression confirmed that successful cardioversion was determined by digoxin use (odds ratio [OR] 0.093, P = .047) and by the interaction between the duration of SR and the (inverse) duration of recurrent AF (OR 6.499, P CONCLUSIONS Flecainide recovers its antiarrhythmic action after cardioversion of AF. However, successful pharmacologic cardioversion occurs only after SR has lasted at least 4 days and is expected only for recurrences having duration of a few hours. Immediate pharmacologic cardioversion of AF recurrence may be a worthwhile strategy for management of persistent AF.

Background: This study was conducted to compare rate- and rhythm-control therapy in patients with persistent atrial fibrillation (AF) and mild to moderate chronic heart failure (CHF). Rate control is not inferior to rhythm control in preventing mortality and morbidity in patients with AF. In CHF, this issue is still unsettled. Methods: In this predefined analysis of the RACE study, a total of 261 patients were in New York Heart Association (NYHA) classes II and III at baseline. These patients were analyzed. The primary end point was a composite of cardiovascular mortality, hospitalization for CHF, thromboembolic complications, bleeding, pacemaker implantation, and life-threatening drug side effects. Furthermore, quality of life was compared. Results: After 2.3 ± 0.6 years, the primary end point occurred in 29 (22.3%) of the 130 rate-control patients and in 32 (24.4%) of the 131 rhythm-control patients. More cardiovascular deaths, hospitalization for CHF, and bleeding occurred under rate control. Thromboembolic complications, drug side effects, and pacemaker implantation were more frequent under rhythm control. Quality of life did not differ between strategies. In patients successfully treated with rhythm control, the prevalence of end points was not different from those who were in AF at study end. However, the type of end point was different: mortality, bleeding, hospitalization for heart failure, and pacemaker implantation occurred less frequently. Conclusions: In patients with mild to moderate CHF, rate control is not inferior to rhythm control. However, if sinus rhythm can be maintained, outcome may be improved. A prospective randomized trial is necessary to confirm these results. © 2005, Elsevier Inc. All rights reserved.

In the RAte Control versus Electrical cardioversion for persistent atrial fibrillation (RACE) study, 522 patients were randomized to either rate or rhythm control therapy. Lone atrial fibrillation (AF) was present in 89 patients. Demographics, cardiovascular mortality and morbidity, and quality of life were compared between patients with lone AF and those with underlying structural heart disease. Patients with lone AF were significantly younger (65 +/- 10 vs 69 +/- 8 years) and had fewer complaints of fatigue (p = 0.01) and dyspnea (p = 0.005). With lone AF, quality-of-life scores were higher on almost all 8 Medical Outcomes Study Short-Form health survey questionnaire subscales, and comparable to healthy, age- and gender-matched controls. Mean follow-up was 2.3 +/- 0.6 years. Cardiovascular end points occurred in 9 patients with lone AF (10%), consisting of death (all bleedings) 3%, thromboembolic complications in 3%, nonfatal bleeding in 2%, and pacemaker implantation in 2%, but no heart failure and severe adverse effects due to antiarrhythmic drugs occurred. End points occurred in 95 patients (22%) with underlying diseases. Heart failure and severe adverse effects from drugs did not occur in patients with lone AF in this study. Despite the absence of demonstrable cardiovascular and cerebrovascular disease, lone AF is associated with bleeding and thromboembolism. (C) 2004 by Excerpta Medica Inc

Spatial ST-vector magnitudes, mod ST/sub 40-80/ mod , were measured every 3 min for at least 3 h after admission, and at wider intervals for 3 days. Likewise, the magnitudes of the difference vector mod Delta QRS mod between the vectorcardiogram (VCG) on admission and a subsequent VCG were determined. The VCG was synthesized from eight electrocardiogram (ECG) leads through linear transformation. The study included 18 patients, only three of whom did not undergo interventions. mod ST/sub 40-80/ mod was always maximal on admission and declined to a stable level in about 4.5. Over the same time span mod Delta QRS mod showed an inconspicuous rise. Correlation of these parameters with infarct size determined by 76 h cumulative serum a-hydroxy-butyrate dehydrogenase activity was poor. Evidently, important ECG charges have already taken place before admission, but even allowing for this, little quantitative relation between VCG parameters and infarct size was apparent. >

Background: Maintenance of sinus rhythm is the main therapeutic goal in patients with atrial fibrillation. However, recurrences of atrial fibrillation and side effects of antiarrhythmic drugs offset the benefits of sinus rhythm. We hypothesized that ventricular rate control is not inferior to the maintenance of sinus rhythm for the treatment of atrial fibrillation. Methods: We randomly assigned 522 patients who had persistent atrial fibrillation after a previous electrical cardioversion to receive treatment aimed at rate control or rhythm control. Patients in the rate-control group received oral anticoagulant drugs and rate-slowing medication. Patients in the rhythm-control group underwent serial cardioversions and received antiarrhythmic drugs and oral anticoagulant drugs. The end point was a composite of death from cardiovascular causes, heart failure, thromboembolic complications, bleeding, implantation of a pacemaker, and severe adverse effects of drugs. Results: After a mean (+/-SD) of 2.3+/-0.6 years, 39 percent of the 266 patients in the rhythm-control group had sinus rhythm, as compared with 10 percent of the 256 patients in the rate-control group. The primary end point occurred in 44 patients (17.2 percent) in the rate-control group and in 60 (22.6 percent) in the rhythm-control group. The 90 percent (two-sided) upper boundary of the absolute difference in the primary end point was 0.4 percent (the prespecified criterion for noninferiority was 10 percent or less). The distribution of the various components of the primary end point was similar in the rate-control and rhythm-control groups. Conclusions: Rate control is not inferior to rhythm control for the prevention of death and morbidity from cardiovascular causes and may be appropriate therapy in patients with a recurrence of persistent atrial fibrillation after electrical cardioversion.

Diagnosing acute Stanford type A aortic dissection with the uncommon involvement of the left main coronary artery(LMCA) remains challenging for the emergency physician because it can resemble acute myocardial infarction with cardiogenic shock. The following case report illustrate this infrequent but critical situation. A 52-year-old woman with a history of hypertension awakened with acute retrosternal chest pain accompanied by nausea and vomiting. She was referred to our hospital for primary coronary intervention because of acute myocardial infarction with cardiogenic shock. Coronary angiography indeed revealed LMCA occlusion. Subsequently successful percutaneous coronary intervention with stent implantation was performed, followed by immediate clinical improvement of the patient. Soon after admission at the coronary care unit, severe chest pain, hypotension, and electrocardiographic signs of diffuse myocardial ischemia relapsed. Control coronary angiography,however, showed no in-stent thrombosis. Review of clinical examination revealed an aortic regurgitation murmur. Because of this dynamic pattern of (1) signs of acute myocardial ischemia, (2) relapse of hemodynamic collapse, and (3) unaltered control coronary angiography together with the confirmed aortic regurgitation at transthoracic echocardiography, the patient was suspected of having aortic dissection. Transesophageal echocardiography revealed Stanford type A aortic dissection with severe eccentric aortic regurgitation and no pericardial effusion. Emergent valve-sparing aortic replacement was performed. The patient recovered completely. In this case, the lifesaving element was primary coronary intervention with stenting of the LMCA preventing extensive myocardial damage followed by a surgical correction of the aorta.

We studied the safety and efficacy of thrombolytic therapy for acute myocardial infarction initiated prior to ambulance transport. Two treatment regimens were compared in a prospective design: 40 patients (group A) received intravenous streptokinase 5 ± 105 IU (SK-IV) prior to and during ambulance transport and were compared with 36 patients (group B) in whom the same dosage of streptokinase was given after arrival in our hospital. In all patients immediate coronary angiography was performed, followed by intracoronary streptokinase administration. Infarct size was assessed by cumulative release of α-hydroxybutyrate dehydrogenase. Apart from three episodes of ventricular fibrillation no procedure-related complications occurred during transport. Median time to SK-IV was 70 minutes in group A versus 125 minutes in group B (P < 0.001). At first visualization the infarct-related vessel was patent in 23 patients (58%) in group A and in 6 patients (17%) in group B (P < 0.001). Anterior wall infarction median infarct size in group A was 32% smaller than that in group B (P < 0.05). We conclude that SK-IV started before ambulance transport is safe, accelerates early reperfusion rate, and consequently leads to a further limitation of infarct size in patients with anterior wall infarction. (J Interven Cardiol 1989:2:3)

The perception of temporal contrasts in speech is known to be influenced by the speech rate in the surrounding context. This rate-dependent perception is suggested to involve general auditory processes since it is also elicited by non-speech contexts, such as pure tone sequences. Two general auditory mechanisms have been proposed to underlie rate-dependent perception: durational contrast and neural entrainment. The present study compares the predictions of these two accounts of rate-dependent speech perception by means of four experiments in which participants heard tone sequences followed by Dutch target words ambiguous between /ɑs/ “ash” and /a:s/ “bait”. Tone sequences varied in the duration of tones (short vs. long) and in the presentation rate of the tones (fast vs. slow). Results show that the duration of preceding tones did not influence target perception in any of the experiments, thus challenging durational contrast as explanatory mechanism behind rate-dependent perception. Instead, the presentation rate consistently elicited a category boundary shift, with faster presentation rates inducing more /a:s/ responses, but only if the tone sequence was isochronous. Therefore, this study proposes an alternative, neurobiologically plausible, account of rate-dependent perception involving neural entrainment of endogenous oscillations to the rate of a rhythmic stimulus.

In a total group of 56 patients with an acute myocardial infarction who were maximally exercised at predischarge, 20 patients (36%) showed greater than or equal to 1 mm asymptomatic ST-T segment depression during exercise. The site of the infarction was anterior in 12 patients and inferior in eight patients. All 20 patients underwent repeated exercise radionuclide angiography 2 days later, 2 hours following oral intake of 120 mg of diltiazem. Double product was not significantly different before and after diltiazem, both at rest and during exercise. Maximal ST-T depression after diltiazem was reduced from 2.3 +/- 0.8 to 0.7 +/- 0.6 mm (p less than 0.01). Left ventricular (LV) ejection fraction at rest before diltiazem was 54.4 +/- 8.7% and after diltiazem was 56.2 +/- 11.3% (p = NS). During exercise, LV ejection fraction improved after diltiazem from 43.2 +/- 12.2% to 49.8 +/- 10.5% (p less than 0.05). Regional wall motion score (1 = normal, 2 = hypokinetic, 3 = akinetic, 4 = dyskinetic) at rest before diltiazem was 9.6 +/- 2.0 and after diltiazem was 9.1 +/- 1.8 (p = NS). During exercise, regional wall motion score improved after diltiazem from 5.8 +/- 1.3 to 4.3 +/- 1.1 (p less than 0.02). We conclude that silent ischemia occurs in a substantial number of patients after myocardial infarction and that diltiazem has acute beneficial effects on asymptomatic ST-T depression and on global and regional LV function in post-infarction patients with silent ischemia.