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IntroductionIn patients with mitral annular disjunction (MAD), it can be difficult to assess the severity of mitral regurgitation (MR), as they present with a prolapsing volume (i.e. volume resulting from mitral valve prolapse, blood volume shift) rather than a regurgitant jet. The influence of the mitral prolapsing volume (MPV) on cardiac dimensions is unknown. We hypothesised that the severity of MR is underestimated in these patients. Our aim was to measure MPV and to investigate its influence on cardiac dimensions in patients with MAD.MethodsWe retrospectively included 131 consecutive patients with MAD from our institution’s echocardiographic database. Transthoracic echocardiography was used to assess MPV. Additionally, we established a control group of 617 consecutive patients with degenerative mitral valve disease and performed propensity score matching.ResultsMedian MPV in the MAD group was 12 ml. MPV was an independent predictor for left ventricular end-diastolic (LVEDD) and end-systolic diameter (LVESD) and left atrial volume (allp 15 ml), LVEDD (56 ± 6 mm vs 51 ± 6 mm,p p p = 0.04] were significantly increased compared to matched patients with degenerative mitral valve disease and similarly assessed severity of MR.ConclusionDue to a volume shift based on the MPV rather than an actual regurgitant jet, MR severity cannot be assessed adequately in MAD patients. Increased MPV induces ventricular and atrial enlargement. These findings warrant future studies to focus on MPV as an additional parameter for assessment of the severity of MR in MAD patients.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): We acknowledge the support from the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation, CVON 2014-9: Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling, and Vascular destabilisation in the progression of AF (RACE V). Unrestricted grant support from Medtronic Trading NL B.V. Background Atrial fibrillation (AF) progression is associated with adverse outcome. The autonomic nervous system plays a yet unsettled role in initiation and progression of AF. Purpose To assess in patients with paroxysmal selfterminating AF differences in phenotype and AF progression depending on the role of the autonomic nervous system in triggering AF episodes. Methods Patients with paroxysmal AF included in the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) study were analysed. Patients were extensively phenotyped at baseline and received continuous rhythm monitoring with an implantable loop recorder (ILR).To adequately define the role of the autonomic nervous system in triggering AF only patients with at least 3 selfterminating AF episodes were included. ILR data were used to assess whether AF was mainly vagally induced (>80% of episodes starting during night time) or mainly adrenergically induced (>80% starting during daytime), and to assess the development of AF progression. If a patient could not be identified as either vagal or adrenergic, they were classified as mixed AF. Primary outcome were differences in AF progression between the three groups. AF progression was defined as (1) progression to persistent or permanent AF, or (2) progression of PAF with >3% burden increase. Follow-up was 2.2 (1.6-2.8) years. Results 278 patients were included, median was age 66 (59-71) years, 117 (42%) were women (Table 1). Patients with vagally or adrenergically induced AF had less comorbidities compared to mixed AF patients (median 2 versus 2 versus 3, respectively, p=0.012). In the mixed group, compared to either the vagal or adrenergic group the estimated glomerular filtration rate was slightly worse (median 78 versus 84 versus 82 mL/min*1.73m2 in the mixed versus vagal and adrenergic group, respectively, p=0.018), diabetes was more common (12% versus 5% versus 0%, respectively, p=0.031). Obesity was most often present in the vagal group (38% versus 12% versus 27%, in the vagal versus adrenergic versus mixed group, respectively p=0.028). Progression rates in the vagal versus adrenergic versus mixed groups were 5% versus 5% versus 24%, respectively (p=0.013 vagal versus mixed and p=0.008 adrenergic versus mixed group, respectively)(Figure). Conclusion Important differences exist between AF patients depending on their autonomic nervous system associated triggering mechanisms. Patients with either vagally or adrenergically induced AF have less comorbidities as compared to those with a mixed initiation type of AF and showed lower AF progression rates.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Dutch Heart Foundation, Medtronic Background Paroxysmal atrial fibrillation (PAF) progression is associated with cardiovascular complications and worse outcome. Obesity is independently associated with AF prevalence and progression. The association between different fat depots in the body with AF is unclear. Aim We aim to systematically investigate the association of different fat depots in the body with AF. Methods 417 patients with PAF and continuous rhythm monitoring (implantable loop recorder or pacemaker) were included in the prospective RACE V study. In addition to extensive phenotyping at baseline including calculating BMI and measuring waist circumference (WC) epicardial and pericardial fat were measured on non-contrast enhanced cardiac CT scans by tracing the pericardium manually on every slice and afterwards fat automatically summed between -50 and -150 HU. Epicardial fat was defined as fat within the pericardium, pericardial fat as fat inside the pericardium and adjacent to the pericardium and thoracic fat as adjacent fat outside the pericardium. AF progression was defined as (1) progression to persistent or permanent AF, or (2) progression of PAF with >3% burden increase within 2.2years of follow-up. Multivariable logistic regression analysis was used to analyse the association of different fat pads with AF progression. Results Six percent of patients per year showed AF progression (51/417) after a median follow-up of 2.2 (1.6-2.8) years. Multivariate analysis identified WC (odds ratio [OR] 1.03, 95% confidence intervals [CI] 1.01-1.06, p=.014) to be associated with AF progression. Epicardial fat (OR 1.00, 95%CI .99-1.01, p=.407), pericardial fat (OR 1.00, 95%CI .99-1.01, p=.311), thoracic fat (OR 1.00, 95%CI .99-1.01, p=.372), and BMI (OR 1.03, 95%CI .97-1.10, p=.328) showed no relation with AF progression. Conclusion AF progression occurred in 6% per year in patients with PAF. In contrast to epicardial, pericardial and thoracic fat measured in a semiautomatic way, WC was the only fat depot associated with AF progression. Whether a more different assessment of obesity and epicardial fat may demonstrate an association with AF progression warrants further study.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Netherlands Organization for Health Research and Development–Health Care Efficiency Research Program Introduction In the Rate Control versus Electrical Cardioversion Trial 7–Acute Cardioversion versus Wait and See (RACE 7 ACWAS) trial an early cardioversion approach was compared to a delayed cardioversion approach for patients with recent-onset symptomatic atrial fibrillation (AF), followed by a four-week monitoring period using mobile health (mHealth). Purpose To evaluate the adherence and motivation to a four-week mHealth prescription to daily intermittent rhythm monitoring for recurrences after emergency department visit in patients with recent-onset AF. In addition, we studied predictors of mHealth adherence and motivation and evaluated whether recurrences during this four-week period influenced adherence and motivation patterns. Methods After the index visit, patients were asked to use an electrocardiographic-based telemetric device to record one minute heart rate and rhythm recordings three times daily and in case of symptoms during a period of four weeks. For patients who collected recordings for more than four weeks, data was censored at four weeks. Adherence and patient motivation based on the number of monitoring days and full monitoring days were evaluated. A p-value of Results 335 patients (58% men; median age 67±11 years) used the telemetric device and were included in the current analysis. The median overall adherence of all patients was 83.3% (IQR 29.9%). The median number of monitoring days was 27 (5), whereas the median number of full monitoring days was 16 (14). Age and the index episode being a recurrent paroxysm of AF rather than a first presentation were identified as independent predictors of adherence (odds ratio (OR) 1.037 (95%CI 1.015-1.060), p=0.001 and OR 1.863 (95%CI 1.190-2.916), p=0.007, respectively). Age (OR 1.031 (95%CI 1.009-1.053), p=0.005) and the use of antiarrhythmic drugs (OR 1.800 (95%CI 1.047-3.093), p=0.033) were identified as independent predictors of motivation. Patients with recurrences had significantly higher median adherence (87.7% vs 81.5%, p=0.028) and more full monitoring days (18 (14) days vs 15 (13) days, p=0.024), and were more likely to perform additional recordings (78.8% vs 49.2%, p= Conclusion Patients with recent-onset AF showed good adherence and motivation to a four-week mHealth prescription to monitor for AF recurrences after an emergency department visit for recent-onset AF. Adherence and motivation were high during the entire monitoring period, indicating that intermittent rhythm monitoring using mHealth is feasible for 1 month. Whether comparable mHealth adherence and motivation can be achieved in real world clinical scenarios outside a randomized study, warrants further observational studies.

Funding Acknowledgements Type of funding sources: None. Introduction In the Rate Control versus Electrical Cardioversion Trial 7–Acute Cardioversion versus Wait and See (RACE 7 ACWAS) trial, a delayed cardioversion approach was compared to early cardioversion. Based on the results of this trial, the delayed cardioversion approach has been added to the European Society of Cardiology guidelines for atrial fibrillation (AF) as a strategy for the acute management of patients with recent-onset AF episodes. Purpose The aim of this study was to evaluate the impact of participation in the RACE 7 ACWAS trial, in combination with education on the delayed cardioversion approach, on the behaviour of patients regarding their recent-onset AF episodes. Methods Patients who were enrolled in the RACE 7 ACWAS trial in our centre and who gave their consent to be approached for future research projects were asked to complete a questionnaire, asking about AF recurrences and related treatment after their participation in the RACE 7 ACWAS trial. Results Of the 148 patients enrolled in the RACE 7 ACWAS trial in our centre, 130 patients were eligible for this study. Of these patients, 16 refused participation, 25 could not be reached and 16 did not return the questionnaire. Seventy-three patients (mean age 69, 64.4% men, 50.7% delayed cardioversion group) completed the questionnaire and were included in the current analysis. Forty-nine patients (67.1%) experienced AF recurrences after the trial. Of the patients with AF recurrences, 23 patients (46%) indicated that since their participation in the trial they have been waiting longer for spontaneous conversion to occur, i.e. 13 patients (26%) wait longer before contacting the emergency department (ED) and 10 patients (20%) wait as long as it takes for spontaneous conversion to occur. Twenty-five patients (51.0%) had been to the ED because of AF at least one time after their participation in the RACE 7 ACWAS trial. Eleven patients (45.8%) who contacted the ED were advised to wait at home a while longer before visiting the ED. In 13 patients (52%) a delayed cardioversion approach at the ED was applied at least once. Eleven patients experiencing recurrences (22.9%) indicated that ED visits had been avoided because the ED advised them telephonically to await spontaneous conversion longer (Figure 1). There were no significant differences between patients who were in the early cardioversion group compared to patients who were in the delayed cardioversion group (Table 1). Conclusion The RACE 7 ACWAS trial appears to have impacted the behaviour of approximately half of the included patients, who indicated that following participation in the trial they were more likely to await spontaneous conversion. Health care professionals at the ED adopted a delayed cardioversion strategy in half of all cases. In about 1 in every 4-5 patients, an ED visit was avoided because patients were telephonically advised to wait longer.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Dutch Heart Foundation, Medtronic Background The incidence of atrial fibrillation (AF) increases exponentially with age. To which extend vascular aging is part of this process is unknown. Pulse wave velocity and carotid intima-media thickness are established markers for vascular aging and have been combined in a vascular aging index as published before(1). Purpose We aim to investigate if vascular age exceeds chronological age in our cohort with paroxysmal AF and if yes to which extend. Methods In this substudy from RACE V we included 295 patients with paroxysmal AF in which carotid-femoral pulse wave velocity (cfPWV) and carotid intima-media thickness (IMT) were measured. To calculate vascular aging we used a logarithmic formula derived from the Malmö-Cancer-and-Diet study which yields a vascular age index derived from cfPWV, cIMT and chronological age. This vascular aging index (VAI) is a strong predictor of cardiovascular events. (1). All patients underwent cardiac echocardiography and had a native cardiac CT scan in which fat around the heart and coronary calcium were quantified. In 121 patients Agatston scores from the ascending aortic artery were also measured. Results Patients in this study had a mean chronological age of 63.8 ± 10.1 years and a vascular age of 71.4 ± 11.7 years. Vascular age was on average 9.3 ± 10.2 years higher than chronological age. Vascular age correlated significantly with markers for diastolic dysfunction, vascular calcification in the coronary arteries as well as the aorta and the amount of epicardial and pericardial fat (table 1). Conclusions In patients with PAF vascular age was on average 9.3 years higher than chronological age in our cohort. Advanced vascular age is represented by vascular and myocardial remodeling related to fibrosis, calcification and fat accumulation. The results suggest that in patients with AF enhanced inflammation is leading to fibrosis and calcification. Whether AF is a marker, a mechanism or both in advanced vascular aging warrants further study.

In the past 20 years the Netherlands-based RACE trials have investigated important concepts in clinical atrial fibrillation (AF). Their scope ranged from rhythm versus rate control to early or delayed cardioversion and also included early comprehensive management of AF in two trials, one focusing on early ‘upstream therapy’ and risk factor management and the other on integrated chronic nurse-led care. Studies were mostly triggered by simple clinical observations including futility of electrical cardioversion in persistent AF; many patients with permanent AF tolerating day-after-day ‘uncontrolled’ resting heart rates of up till 110 beats/min; patients being threatened more by vascular risks than AF itself; and insufficient guideline-based treatments for AF. Also the observation that recent-onset atrial fibrillation generally converts spontaneously, obviating cardioversion, triggered one of the studies. The RACE trials shifted a number of paradigms and by that could change the AF guidelines. The initial ‘shock-and-forget’ attitude made place for increased attention for anticoagulation, and in turn, broader vascular risks were recognised. In a nutshell, the adage eventually became: ‘look beyond the ECG, treat the patient’. Electronic supplementary material The online version of this article (10.1007/s12471-020-01476-0) contains supplementary material, which is available to authorized users.

Background Contemporary data regarding the characteristics, treatment and outcomes of patients with atrial fibrillation (AF) are needed. We aimed to assess these data and guideline adherence in the EURObservational Research Programme on Atrial Fibrillation (EORP-AF) long-term general registry. Methods We analysed 967 patients from the EORP-AF long-term general registry included in the Netherlands and Belgium from 2013 to 2016. Baseline and 1‑year follow-up data were gathered. Results At baseline, 887 patients (92%) received anticoagulant treatment. In 88 (10%) of these patients, no indication for chronic anticoagulant treatment was present. A rhythm intervention was performed or planned in 52 of these patients, meaning that the remaining 36 (41%) were anticoagulated without indication. Forty patients were not anticoagulated, even though they had an indication for chronic anticoagulation. Additionally, 63 of the 371 patients (17%) treated with a non-vitamin K antagonist oral anticoagulant (NOAC) were incorrectly dosed. In total, 50 patients (5%) were overtreated and 89 patients (9%) were undertreated. However, the occurrence of major adverse cardiac and cerebrovascular events (MACCE) was still low with 4.2% (37 patients). Conclusions Overtreatment and undertreatment with anticoagulants are still observable in 14% of this contemporary, West-European AF population. Still, MACCE occurred in only 4% of the patients after 1 year of follow-up.

Background Women are usually underrepresented in studies evaluating rhythm control strategies in patients with atrial fibrillation (AF). Subsequently, the same holds true for studies looking at predictors for success of a rhythm control strategy for AF. Purpose To study the predictive power of the non-invasively determined dominant frequency (DF) on the electrocardiogram (ECG) in men and women undergoing electrical cardioversion (ECV) for persistent AF. Methods We matched 105 female patients undergoing elective ECV for persistent AF and 105 male control patients based on age and cardiovascular comorbidity profile. We determined the DF on all 12 leads of a standard digital 10 seconds ECG recorded on the day of ECV. Recurrences of AF within the first year after ECV were documented. Results There were no differences in comorbidities, AF duration, left ventricular systolic function, indexed left atrial volume and anti-arrhythmic drugs between male and female patients. The dominant frequency was significantly lower in male patients without an AF recurrence on all leads. The best performing lead to identify patients with recurrences was lead III with an AUC 0.752. The optimal cut-off point was a DF Conclusion The non-invasively measured dominant frequency is able to predict AF recurrence after electrical cardioversion in male patients with persistent AF but not in a matched female cohort. This difference might be explained by different pathophysiological mechanisms underlying AF in male and female patients. Therefore, future research is needed on pathophysiological differences between men and women that can explain and might overcome these challenges. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Network for Translational Research in Atrial Fibrillation (grant no. 261057), the Center for Translational Molecular Medicine (COHFAR)

Background Cardioversion is commonly performed prior to antiarrhythmic drug initiation for atrial fibrillation/flutter (AF). There are limited data describing baseline differences in patients requiring cardioversion to maintain sinus rhythm compared to those who do not. Likewise, response to antiarrhythmic drugs, including dronedarone, specifically in patients requiring cardioversion has not been well defined. Purpose To evaluate efficacy and safety of dronedarone versus placebo in patients with non-permanent AF who had cardioversion within 5 days prior to randomization in EURIDIS/ADONIS. Methods To qualify for enrolment in EURIDIS/ADONIS patients were required to be in sinus rhythm for at least 1 hour preceding randomization. Of 1237 patients randomized (2:1 dronedarone to placebo), 364 needed cardioversion for study entry (dronedarone 243, placebo 121). AF recurrence was evaluated by ECG obtained during study visits, scheduled transtelephonic monitoring, or at symptom recurrence. Results Cardioversion patients were more likely to have rheumatic heart disease, valvular heart disease, any structural heart disease, and heart failure. Nonetheless, the median time to 1st AF recurrence was longer for dronedarone versus placebo both in cardioversion patients (50 versus 15 days, hazard ratio 0.76, 95% CI 0.59, 0.97) and no cardioversion patients (150 versus 77 days, hazard ratio 0.76, 95% CI 0.64, 0.90), as was time to 1st symptomatic recurrence (cardioversion: 347 versus 87 days, hazard ratio 0.65, 95% CI 0.49, 0.87; no cardioversion: 288 versus 120 days, hazard ratio 0.74, 95% CI 0.62, 0.90) (Figure 1). There was a trend towards fewer 1st AF hospitalizations within 12 months for dronedarone versus placebo (7.8 versus 12.4%, hazard ratio 0.60, 95% CI 0.31, 1.18 in cardioversion patients; 8.4 versus 10.4%, hazard ratio 0.74, 95% CI 0.47, 1.17 in no cardioversion patients). In cardioversion patients, rates of treatment-emergent adverse events with dronedarone versus placebo were 64 versus 66%, serious treatment-emergent adverse events were 19 versus 26%, permanent discontinuations were 9 versus 6%, and deaths were 0 versus 1%. Conclusions 1) Cardioversion-requiring patients have more baseline structural heart disease and overall shorter time to AF recurrence. 2) Dronedarone effectively delayed 1st AF recurrence versus placebo in patients with or without recent cardioversion. 3) Safety of dronedarone in cardioversion patients was similar to placebo and overall observations from EURIDIS/ADONIS despite baseline differences in comorbidities. Acknowledgement/Funding Sanofi, New York, New York, United States of America

Aims Great heterogeneity in rhythm control management of patients with atrial fibrillation (AF) has been described. The aim of this study was to investigate how selective the patient cohort referred for AF ablation is, as compared to the general AF population in Europe, and to describe the governing mechanisms for such selection. Methods Descriptive comparative statistical analyses of the baseline characteristics were performed between the cohorts of Atrial Fibrillation Ablation Long-Term (ESC-EORP EHRA AFA-LT) Registry, designed to provide a picture of contemporary real-world AF ablation, and the AF population from the AF-General (ESC-EORP EHRA AF-Gen) PilotRegistry. Data collection was performed using a web-based system. Results In the AFA and in the AFG pilot registries 3593 and 3049 patients were enrolled, respectively. Patients who underwent AF ablation were younger,more commonly male, and had significantly less co-morbidities. Lone AF was predominant in AFA patients who were at lower risk of stroke (CHA2DS2-VASc >5: 2.9% vs. 24.5%, all P1 and more prevalentAF-related symptoms such as palpitations, fatigue and weakness (all p Conclusions The comparison of the patient chorts in the AFA and AFG registries showed that AF ablation in European clinical practice is mostly performed in relatively young, symptomatic and otherwise relatively healthy patients. Acknowledgement/Funding Abbott Vascular Int.; Amgen Cardiovascular, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb and Pfizer Alliance

Introduction: The importance of gut microbiome in cardiovascular disease has been increasingly recognized. Trimethylamine N-oxide (TMAO) is a gut microbe-derived metabolite that is associated with cardiovascular disease, including atrial fibrillation (AF). The role of TMAO in clinical AF progression however remains unknown.Methods and results: In this study we measured TMAO and its precursor (betaine, choline, and L- carnitine) levels in 78 patients using plasma samples from patients that participated in the AF-RISK study. 56 patients suffered from paroxysmal AF and 22 had a short history of persistent AF. TMAO levels were significantly higher in patients with persistent AF, as compared to those with paroxysmal AF (median [IQR] 5.65 [4.7-9.6] m/z versus 4.31 [3.2-6.2] m/z, p < 0.05), while precursor levels did not differ. In univariate analysis, we observed that for every unit increase in TMAO, the odds for having persistent AF increased with 0.44 [0.14-0.73], p < 0.01. Conclusion: These results suggest that higher levels of TMAO are associated with more progressed forms of AF. We therefore hypothesize that increased TMAO levels may reflect disease progression in humans. Larger studies are required to validate these preliminary findings.Trial Registration number: Clinicaltrials.gov NCT01510210.

Background The fundoscopic examination of hypertensive patients, which is an established hypertension-related target organ damage (TOD), tends to be underutilized in clinical practice. We sought to investigate the relationship between retinal alterations and left atrium (LA) volumes by means of real-time, three-dimensional echocardiography (RT3DE), which is the most pivotal predictor of diastolic dysfunction. Methods Our population consisted of 88 consecutive essential hypertensive patients (age 59.2 ± 1.2 years, 53 females) without overt cardiovascular disease. All subjects underwent a fundoscopy examination and were distributed into five groups according to the Keith-Wagener-Barker (KWB) classification. Comprehensive transthoracic echocardiographic and RT3DE measurements were performed to assess LA volumes and phasic functions. Results The four groups (KWB grades 0-4: including 26, 20, 26, and 16 patients, respectively) did not differ with regards to age, gender, or metabolic profile. There were no significant differences between groups with regards to parameters reflecting left ventricle (LV) systolic function and diastolic dysfunctions in conventional echocardiography, except isovolemic relaxation time (IVRT) and deceleration time (DT). Nevertheless, patients in the higher KWB category had higher values of LA volumes (LA maximal volume, LA minimal volume, preatrial contraction volume, LA total stroke volume, LA active stroke volume, p< 0.001) regarding RT3DE (table 1). There is also a significant relationship between preatrial contraction volume and duration of HT (r: 0.67, p

Background / Objectives. Atrial fibrillation (AF) is a very frequent and complex disease often associated with other medical conditions. The Euro Heart Survey (EHS) on AF showed that adherence to guidelines may reduce morbidity and mortality in AF patients. Therefore a nurse-driven, guideline-based, ICT-supported integrated chronic care program (ICCP) was developed and implemented in daily practice. The objective of this study is to evaluate the clinical feasibility of the ICCP, with guideline adherence as the endpoint. Methods. 111 ambulant patients referred for treatment of their AF were enrolled in the ICCP. In this group, patients underwent standardised clinical testing and were subsequently managed by a nurse, supported by a dedicated ICT program and supervised by cardiologists. For comparison, we used a recent historical control group of 102 patients who participated in the Maastricht part of the Euro Heart Survey (EHS) on AF. Results. Guideline adherence was excellent within the ICCP and compared favourably with the EHS-AF data concerning both clinical testing (trigger factors recorded in 100 vs. 44%; echocardiogram performed in 99 vs. 88%; thyroid-stimulating hormone level recorded in 96% vs. 63%) as well as treatment (antithrombotic therapy in 90 vs. 78%; rhythm control avoided in completely asymptomatic patients in 100 vs. 54%; class I drugs avoided in patients with structural heart disease in 90 vs. 95%; rhythm control avoided in permanent AF patients in 100 vs. 92%). Conclusion. The high level of guideline adherence suggests that a nurse-driven, guideline-based, ICT-supported ICCP for AF patients is feasible. (Neth Heart J 2010;18:471–7.)

Background: Experimental and clinical evidence suggests that calcium-channel blockers may retard the atherosclerotic process after long-term treatment. Whether these effects exist after intermediate-term treatment in hypertensive patients is mainly unknown. Objective: To determine the 26-week effects of the long-acting calcium-channel blocker nifedipine on intima media thickness (IMT) in newly found hypertensive patients. Design: Open-label study with blinded end-point analysis. Methods: From a population survey, 131 previously untreated mild hypertensives (4 x systolic blood pressure between 160 and 220 mmHg and/or diastolic blood pressure between 95 and 115 mmHg) were included. Patients were treated with long-acting nifedipine 30-60 mg targeted to reach a predetermined drop in blood pressure. Prior to and after 26 weeks of treatment, IMT was measured by ultrasonography in the carotid and femoral artery. The combined mean maximal far wall IMT was used as primary endpoint. Change from baseline was evaluated by paired t-test in an intention-to-treat analysis. Results: The mean maximal far wall IMT at baseline was 1.03 +/- 0.23 mm, and decreased by 0.078 mm (95% confidence interval, CI 0.044-0.111) after treatment. Regression analysis, including baseline IMT and changes of blood pressure, showed that reduction of IMT was mostly influenced by baseline IMT (p

Atrial Remodeling in Tachycardiomyopathy. Introduction: Atrial fibrillation (AF) and congestive heart failure (CHF) are two clinical entities that often coincide. Our aim was to establish the influence of concomitant high ventricular rate and consequent development of CHF on electrical remodeling and dilation during atrial tachycardia. Methods and Results: A total of 14 goats was studied. Five goats were subjected to 3:1 AV pacing (A-paced group, atrial rate 240 beats/min, ventricular rate 80 beats/min). Nine goats were subjected to rapid 1:1 AV pacing (AV-paced group, atrial and ventricular rates 240 beats/min). During 4 weeks, right atrial (RA) and left ventricular (LV) diameters were measured during sinus rhythm. Atrial effective refractory periods (AERP) and inducibility of AF were assessed at three basic cycle lengths (BCL). After 4 weeks of rapid AV pacing, RA and LV diameters had increased to 151% and 113% of baseline, whereas after rapid atrial pacing alone, these parameters were unchanged. Right AERP (157 +/- 10 msec vs 144 +/- 16 msec at baseline with BCL of 400 msec in the A-paced and AV-paced group, respectively) initially decreased in both groups, reaching minimum values within 1 week. Subsequently, AERP partially recovered in AV-paced goats, whereas AERP remained short in A-paced goats (79 7 msec vs 102 12 msec after 4 weeks; P

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.

Objectives. To assess the prevalence of microalbuminuria in the general population, especially in nondiabetic and nonhypertensive subjects, and its association with known cardiovascular risk factors and cardiovascular morbidity. Design. Cross-sectional cohort study. Setting. Inhabitants of the city of Groningen, the Netherlands. Subjects. All inhabitants, aged between 28 and 75 years, were send a postal questionnaire and a vial to collect an early morning urine sample (n = 85 421). Of these 40 856 subjects (47.8%) responded. Cardiovascular risk factors and morbidity were validated in a well defined nondiabetic and nonhypertensive group of 5241 subjects. Main outcome measures. Microalbuminuria, self-reported cardiovascular risk and cardiovascular morbidity in the total study cohort, and additionally more detailed measurements in a subset of the total population. Results. Microalbuminuria (20-200 mg L-1) was present in 7.2% of the subjects and independently associated with age, gender, hypertension, diabetes, smoking, previous myocardial infarction and stroke. Some of these associations were already observed at albuminuria levels of 10-20 mg L-1. After exclusion of the diabetic and hypertensive subjects, microalbuminuria was still prevalent in 6.6% of the subjects. Conclusions. Microalbuminuria appears to be common not only in the general population but also in a nondiabetic, nonhypertensive population and is independently associated with increased cardiovascular risk factors and cardio-vascular morbidity. Importantly, some of these associations are present at urinary albumin levels currently considered to be normal. These findings suggest that urinary albumin measurements may be useful in early risk profiling and prevention of cardiovascular disease in the population at large.

Background —Sustained shortening of the atrial effective refractory period (AERP), probably due to reduction in the L-type calcium current, is a major factor in the initiation and maintenance of atrial fibrillation (AF). We investigated underlying molecular changes by studying the relation between gene expression of the L-type calcium channel and potassium channels and AERP in patients with AF. Methods and Results —mRNA and protein expression were determined in the left and right atrial appendages of patients with paroxysmal (n=13) or persistent (n=16) AF and of 13 controls in sinus rhythm using reverse transcription polymerase chain reaction and slot-blot, respectively. The mRNA content of almost all investigated ion channel genes was reduced in persistent but not in paroxysmal AF. Protein levels for the L-type Ca 2+ channel and 5 potassium channels (Kv4.3, Kv1.5, HERG, minK, and Kir3.1) were significantly reduced in both persistent and paroxysmal AF. Furthermore, AERPs were determined intraoperatively at 5 basic cycle lengths between 250 and 600 ms. Patients with persistent and paroxysmal AF displayed significant shorter AERPs. Protein levels of all ion channels investigated correlated positively with the AERP and with the rate adaptation of AERP. Patients with reduced ion channel protein expression had a shorter AERP duration and poorer rate adaptation. Conclusions —AF is predominantly accompanied by decreased protein contents of the L-type Ca 2+ channel and several potassium channels. Reductions in L-type Ca 2+ channel correlated with AERP and rate adaptation, and they represent a probable explanation for the electrophysiological changes during AF.

Myocardial blood flow (MBF) reserve is impaired in patients with symptomatic chronic heart failure. Whether this is already present in asymptomatic left ventricular (LV) dysfunction, and whether it is affected by angiotensin converting enzyme (ACE) inhibition, is unknown. We examined MBF in 20 patients with asymptomatic LV dysfunction and compared them to healthy volunteers. MBF (reserve) was assessed with positron emission tomography (PET) and N-13 ammonia at rest, during dipyridamole stress test (DST) and during cold pressor test (CPT). Further, in the LV-dysfunction group, we studied the effects of 3 months treatment with ACE inhibition with a second PET study. Patients were randomized double-blind to perindopril 4 mg daily or placebo. MBF at rest was similar in controls and patients. DST-induced MBF reserve, however, was decreased in patients vs. controls (1.71 ± 0.2 vs. 2.62 ± 0.5, respectively p < 0.05). Also CPT-induced MBF was lower in patients (1.14 ± 0.06 vs. 1.23 ± 0.03, p < 0.05). After 3 months double-blind treatment, CPT-induced MBF decreased in the placebo group (from 1.12 ± 0.02 to 0.93 ± 0.06), but was preserved in the perindopril group (from 1.16 ± 0.08 to 1.14 ± 0.08 shifts from baseline: −0.19 ± 0.05 vs. −0.02 ± 0.07 respectively p = 0.07). This was compatible with a trend to a smaller increase in coronary vascular resistance during CPT (1.23 ± 0.08 vs. 1.03 ± 0.06, placebo vs. perindopril, p = 0.06). In patients with asymptomatic LV dysfunction, MBF, both after vasodilation and after CPT, is already impaired. ACE inhibition with perindopril during this short-term treatment had no significant effects.

Background This study tested the hypothesis that statins may reduce left ventricular hypertrophy (LVH) in patients with hypertension and LVH. Method A prospective randomised open-label study with blinded endpoints assessment was performed in 142 patients. Inclusion criteria were hypertension, left ventricular ejection fraction ≥50% and echocardiographic determined LVH, defined as a left ventricular mass index (LVMI) of ≥100g/m 2 in women and ≥116g/m 2 in males. Patients were randomised between rosuvastatin 20mg once daily vs control. For each patient an echocardiogram and blood samples were obtained. These tests were repeated after 6months. Results Baseline characteristics: mean age was 62±11year and 62 (44%) were male. In both groups, there was a non-significant reduction in LVMI: 118±22 to 111±19g/m 2 in the control group and 118±21 to 114±22 in the rosuvastatin group ( p =0.376 for the comparison between rosuvastatin and control after 6months). After six months, LDL-cholesterol was reduced from 3.5±1.0 to 2.1±1.2mmol/L (40% reduction) in the rosuvastatin group and remained unchanged in the control group (3.5±0.9 vs 3.6±0.9mmol/L. Hs-CRP decreased more with rosuvastatin compared to control (−38% vs −15%, p =0.006) There was no significant reduction in NT-pro-BNP levels after 6months. Conclusion Rosuvastatin does not reduce LVH despite a large LDL reduction in patients with hypertension and LVH.

OBJECTIVES We sought to investigate the effect of angiotensin-converting enzyme (ACE) inhibition

Mini-Maze and Mitral Valve Surgery. Introduction: After mitral valve (MV) surgery, preoperative atrial fibrillation (AF) often recurs while cardioversion therapy generally fails. Additional Cox maze surgery improves postoperative arrhythmia outcome, but the extensive nature of such an approach limits general appliance. We investigated the clinical outcome of a simplified, less extensive Cox maze procedure ("mini-maze") as adjunct to MV surgery. Methods and Results: Thirteen patients with MV disease and preoperative AF were treated with combined surgery (group 1). Nine control patients without previous AF underwent isolated MV surgery (group 2), We retrospectively compared the results to findings in 23 patients with preoperative AF who had undergone isolated MV surgery (group 3), In group 1, mini-maze took an additional 46 minutes of perfusion time. One 75-year-old patient died of postoperative multiple organ failure. Seven patients showed spontaneously converting (within 2 months) postoperative AF. After 1 year, 82% were in sinus rhythm (SR), No sinus node dysfunction was observed, In group 2, all patients were in SR after 1 year, In group 3, only 53% were in SR after 1 year, despite serial cardioversion and antiarrhythmic drug therapy. Exercise tolerance and heart rate were comparable for groups 1 and 2, Left atrial function was present in all but one patient in group 1 and in all patients in group 2 (after MV reconstruction). Conclusion: Adding a relatively simple mini-maze to MV surgery improves arrhythmia outcome in patients with preoperative AF without introducing sinus node dysfunction or persistent absence of left atrial function. The results of this type of combined surgery are encouraging and deserve further attention.

Aims To examine whether the presence, or development, of atrial fibrillation in patients with advanced chronic heart failure, is associated with a poorer prognosis, compared to patients with sinus rhythm and chronic heart failure. Methods and Results We examined 409 patients with moderate to severe chronic heart failure, and compared patients with sinus rhythm (n=325) to those with atrial fibrillation (n=84). At baseline, the two groups were similar regarding most indices of severity of chronic heart failure, such as left ventricular ejection fraction (0·23) and New York Heart Association (NYHA) functional class, while they were different for age (70 years for atrial fibrillation vs 67 years for sinus rhythm patients), aetiology of chronic heart failure, blood pressure, concomitant treatment, and plasma neurohormones (all P

We evaluated the role of SH-groups in improvement of endothelial dysfunction with ACE-inhibitors in experimental heart failure. To this end, we compared the vasoprotective effect of chronic treatment with zofenopril (plus SH-group) versus lisinopril (no SH-group), or N-acetylcysteine (only SH-group) in myocardial infarcted (MI) heart failure rats. After 11 weeks of treatment, aortas were obtained and studied as ring preparations for endothelium-dependent and -independent dilatation in continuous presence of indomethacin to avoid interference of vasoactive prostanoids, and the selective presence of the NOS-inhibitor L-NMMA to determine NO-contribution. Total dilatation after receptor-dependent stimulation with acetylcholine (ACh) was attenuated (−49%, P

OBJECTIVESWe sought to study the influence of frequency of exercise training during cardiac rehabilitation on functional capacity (i.e., peak oxygen consumption [VO2] and ventilatory anaerobic threshold [VAT]) and quality of life (QoL).BACKGROUNDAlthough the value of cardiac rehabilitation is now well established, the influence of the different program characteristics on outcome has received little attention, and the effect of frequency of exercise training is unclear. Functional capacity is regularly evaluated by peak VO2 but parameters of submaximal exercise capacity such as VAT should also be considered because submaximal exercise capacity is especially important in daily living.METHODSPatients with coronary artery disease (n = 130, 114 men; mean age 52 ± 9 years) were randomized to either a high- or low-frequency program of six weeks (10 or 2 exercise sessions per week of 2 h, respectively). Functional capacity and QoL were assessed before and after cardiac rehabilitation. Global costs were also compared.RESULTSCompared with baseline, mean exercise capacity increased in both programs: for high- and low-frequency, respectively: peak VO2 = 15% and 12%, Wmax = 18% and 12%, VAT = 35% and 12% (all p < 0.001). However, when the programs were compared, only VAT increased significantly more during the high-frequency program (p = 0.002). During the high-frequency program, QoL increased slightly more, and more individuals improved in subjective physical functioning (p = 0.014). We observed superiority of the high-frequency program, especially in younger patients. Mean costs were estimated at 4,455 and 2,273 Euro, respectively, for the high- and low-frequency programs.CONCLUSIONSHigh-frequency exercise training is more effective in terms of VAT and QoL, but peak VO2 improves equally in both programs. Younger patients seem to benefit more from the high-frequency training.

The QUO VADIS (the effects of QUinapril On Vascular Ace and Determinants of ISchemia) study was a randomized, double-blind, placebo-controlled trial designed to evaluate the effects of long-term angiotensin-converting enzyme (ACE) inhibition on angiotensin II formation in human vasculature. Patients (n = 187) scheduled for coronary artery bypass surgery used study medication 27 +/- 1 days before surgery. Segments of internal mammary arteries were exposed to increasing doses (0.1 nM-1 microM) of angiotensin I and II in organ baths. The rate of local angiotensin II formation is a function of the reciprocal of the difference between the pEC50's of the dose response curves to angiotensin I and II (-log/mol) and of the area between the curves (units). Quinapril (40 mg) and captopril (3 x 50 mg) similarly and significantly reduced mean blood pressure compared with placebo (p = 0.04). Difference between pEC50's was 0.90 +/- 0.08 in quinapril patients compared with 0.60 +/- 0.08 for placebo (p = 0.01); the area between curves was 91 +/- 8 for quinapril patients compared with 67 +/- 8 for placebo (p = 0.03). Angiotensin II formation was decreased to a lesser extent with captopril and was not statistically different from placebo (p = 0.3); the difference between pEC50's was 0.83 +/- 0.15; the area between curves was 84 +/- 12. This is the first randomized study to demonstrate that long-term oral treatment with an ACE inhibitor reduces vascular angiotensin II formation in humans.

Conversion of atrial flutter and atrial fibrillation (AF) can be achieved by either pharmacologic or direct-current (DC) electrical cardioversion. DC electrical cardioversion is more effective and restores sinus rhythm instantaneously; however, general anesthesia is necessary, which can cause severe complications. On the other hand, pharmacologic cardioversion is less effective. First, time to conversion is unpredictable and may be relatively long, especially with oral drug therapy. Also, the rate of conversion is lower and depends on duration of AF. In addition, safety is an important issue. Adverse drug reactions include bradycardia, paradoxical tachycardia due to enhanced atrioventricular conduction, ventricular proarrhythmia, and acute heart failure. In paroxysmal AF, drug therapy is usually aimed at an acute conversion. Class IA and IC drugs are more efficacious than the class III drugs sotalol, amiodarone, and ibutilide. By contrast, class III drugs are more effective for the conversion of atrial flutter. Acute conversion out-of-hospital ("pill in the pocket approach") should be done only if the drug used appeared effective and safe after a few in-hospital trials. In persistent AF, DC conversion is preferred because drugs are particularly ineffective if the arrhythmia has lasted >24-48 hours. The latter probably relates to electrical and anatomical remodeling of the atria during ongoing atrial fibrillation and flutter. Nevertheless, a wait-and-see approach using, for example, oral amiodarone may be adopted with late DC conversion if the drug fails to convert persistent AF. However, the consequences of remodeling seem to dictate an early conversion. In this respect, echocardiography-guided DC cardioversion may become increasingly important in AF. It will prevent treatment resistance and potentially reduces embolic complications. In a hybrid approach, antiarrhythmic drugs may be used to enhance DC conversion and prevent (sub)acute recurrences of AF. However, it may increase the defibrillation threshold, especially if class IC drugs are used. New treatment options such as automatic defibrillation (implantable atrioverter) are still investigational.

The present study assessed the reoccurrence of myocardial ischemia after withholding electrical neurostimulation. After randomization, in the study or withdrawal group, spinal cord stimulation (SCS) was set active during the first 4 weeks, followed by 4 weeks of withholding stimulation. In the control group, SCS was switched off during 4 weeks before the end of the study. The control group had no crossover period. Measurements were done at baseline, then after 4 and 8 weeks. The first periods at 4 weeks of each sequence of both groups were compared. In addition, a comparison of clinical variables was performed between the study group 4 weeks after withholding stimulation and the control group 4 weeks following randomization. A total number of 24 patients with refractory angina and an implanted spinal cord stimulator were included in the study (n = 12) and control group. Angina pectoris complaints, nitroglycerin intake, ischemia, and heart rate variability using 48-hour ambulatory electrocardiographic monitoring were assessed. In addition, neurohormonal status and symptom-limited aerobic capacity were evaluated. There was no increase of anginal complaints or ischemia after withholding stimulation. Neurohormonal levels and aerobic capacity were not altered. We conclude that there is no adverse clinical rebound phenomenon after withholding neurostimulation in patients with refractory angina pectoris.

Focal Atrial Fibrillation and Electrical Remodeling. Although atrial fibrillation- (AF) induced changes in atrial refractoriness (atrial electrical remodeling) have been demonstrated in a number of different animal models, the clinical significance of this process is unknown. We describe a patient in whom there has been documented progression of atrial ectopy to persistent AF accompanied by evidence of atrial electrical remodeling, with reversal of remodeling following successful ablation of the focal source of AF. A second patient with focal AF, but with a "nonfocal" appearance on the ECG, is also described. These cases illustrate: (1) the possibility that a significant proportion of younger patients with idiopathic persistent AF may well ha re a focal source as the underlying abnormality; and (2) atrial electrical remodeling reverses following ablation of the underlying source.

The effect of beta blockade on heart rate in patients with either idiopathic or ischemic cardiomyopathy was studied. It was found that beta blockade reduced the early morning increase in heart rate to a greater extent in patients with idiopathic dilated cardiomyopathy than in those with ischemic dilated cardiomyopathy.

Objectives. To determine dose-related clinical and neurohumoral effects of angiotensin-converting enzyme (ACE) inhibitors in patients with chronic heart failure (CHF), we conducted a double-blind, placebo-controlled, randomized study of three doses (2.5 mg, 5 mg and 10 mg) of the long-acting ACE inhibitor imidapril. Background. The ACE inhibitors have become a cornerstone in the treatment of CHF, but whether high doses are more effective than low doses has not been fully elucidated, nor have the mechanisms involved in such a dose-related effect. Methods. In a parallel group comparison, the effects of three doses of imidapril were examined. We studied 244 patients with mild to moderate CHF (New York Heart Association class II–III: ±80%/20%), who were stable on digoxin and diuretics. Patients were treated for 12 weeks, and the main end points were exercise capacity and plasma neurohormones. Results. At baseline, the four treatment groups were well-matched for demographic variables. Of the 244 patients, 25 dropped out: 3 patients died, and 9 developed progressive CHF (3/182 patients on imidapril vs. 6/62 patients on placebo, p Conclusions. Already within 3 months after treatment initiation, high-dose ACE inhibition (with imidapril) is superior to low-dose. This is reflected by a more pronounced effect on exercise capacity and some of the neurohormones, but it does not appear to be related to the extent of suppression of plasma ACE.

There are conflicting reports on the interaction of aspirin with angiotensin-converting enzyme inhibitors in heart failure and systemic hypertension. A past hoc analysis of the Captopril and Thrombolysis Study (CATS) study was conducted. At randomization, 94 patients (31.5%) took aspirin. In patients who took aspirin, the cumulative alpha-hydroxy butyrate dehydrogenase release was 1,151 +/- 132 IU/L in patients randomized to captopril compared with 1,401 +/- 136 IU/L in patients randomized to placebo (difference -250 +/- 189 [95% confidence interval (CI) -620 to 120]). This difference was comparable to the difference in patients who did not use aspirin (-199 +/- 147 [95% CI -488 to 897]). One year after acute myocardial infarction, an increase in left ventricular end-diastolic volume index of 2.2 +/- 3.0 ml/m(2) in captopril-treated and 1.9 +/- 2.9 ml/m(2) in placebo-treated patients was observed in patients who took aspirin (difference 0.4 +/- 4.2 [95% CI -8.2 to 8.9]), This difference was also comparable to the difference in patients who did not take aspirin (2.2 +/- 3.8 [95% CI -5.2 to 9.7]). One year after acute myocardial infarction, patients who did take aspirin had a mean change in LV end-diastolic volume index of 2.1 +/- 2.1 ml/m(2) compared with 8.4 +/- 1.9 ml/m(2) in patients who did not use aspirin (p = 0.02), Thus, aspirin does not attenuate the acute and long-term effects of angiotensin-converting enzyme inhibition after acute myocardial infarction, but independently reduces LV dilation after myocardial infarction. (C) 1998 by Excerpta Medica, Inc.

Over the past decade, various studies have demonstrated that class I antiarrhythmic drugs should be avoided in patients with heart failure, cardiac ischaemia or a previous myocardial infarction. In contrast, class II drugs (beta-blockers) reduce morbidity and may even lower mortality in patients suffering from moderate to severe heart failure. In these patients, careful titration of the drug dosage, frequently during hospital admission, may be necessary. If in the setting of heart failure ventricular arrhythmias are symptomatic and/or sustained, patients can be treated effectively, after appropriate treatment of the underlying disease, with the class III drug amiodarone. Unfortunately, this drug does not lower overall mortality, implying that prophylactic institution of amiodarone is not indicated. Pure class III antiarrhythmic drugs like d-sotalol, ibutilide and dofetilide show a high rate of torsade de pointes. Currently, only ibutilide has been approved for clinically monitored intravenous administration. Class IV drugs, the calcium channel blockers, are still very useful for rate control of atrial fibrillation and conversion or prevention of atrioventricular nodal re-entrant tachycardias and circus movement tachycardias using a (concealed) bypass tract. Finally, an implantable cardioverter defibrillator seems to improve overall survival in patients with life-threatening ventricular arrhythmias. This may imply that an increasing number of patients will be candidates for such a device. However, it will be necessary to await publication of data involving these devices from current ongoing studies.

Heart failure is often complicated by atrial fibrillation. Once atrial fibrillation has started it further enhances heart failure due to uncontrolled rate with shortened filling time and provocation of tachycardiomyopathy. Absent atrial kick and irregularity of the ventricular rhythm also contribute. Considering these mechanisms, restoration of sinus rhythm is most beneficial but is associated with frequent recurrences. Before cardioversion heart failure must be treated. ACE inhibition, initiated before cardioversion, may enhance maintenance of sinus rhythm by reducing neurohumoral activation. As a consequence, arrhythmogenic factors diminish and ventricular function may improve. beta-blockade and amiodarone may have similar effects. If cardioversion fails, adequate rate control is mandatory to prevent progressive ventricular dysfunction. Digitalis is the treatment of first choice, but when the heart rate remains uncontrolled low-dose beta-blockade should be given. If the ventricular rate remains uncontrolled despite drugs, atrioventricular node ablation with implantation of a pacemaker may be considered. Not only patients with idiopathic heart failure and atrial fibrillation, but also those with significant underlying heart disease may benefit from this intervention. In atrial fibrillation patients undergoing cardiac surgery for heart failure due to valvular disease, additional arrhythmia surgery may be contemplated.

OBJECTIVE: Angina and the presence of myocardial ischaemia are common in hypertrophic cardiomyopathy. Dual chamber pacing results in clinical improvement in these patients. This study evaluates the effects of permanent dual chamber pacing on absolute regional myocardial perfusion and perfusion reserve. SETTING: University hospital. PATIENTS AND DESIGN: Six patients with hypertrophic cardiomyopathy and severe symptoms of angina received a dual chamber pacemaker. Absolute myocardial regional perfusion and perfusion reserve (dipyridamole 0.56 mg/kg) were measured by dynamic positron emission tomography with 13N-ammonia both during sinus rhythm and 3 months after pacemaker insertion. Results were compared with those from 28 healthy volunteers. RESULTS: Pacing resulted in a reduction of anginal complaints and a reduction in intraventricular pressure gradient from 65 (SD 30) mm Hg to 19 (10) mm Hg. During sinus rhythm, baseline perfusion was higher in patients with hypertrophic cardiomyopathy than controls (184 (31) v 106 (26) ml/min/100 g, P < 0.01), and perfusion reserve was lower (1.6 (0.4) v 2.8 (1.0), P < 0.05). During pacing myocardial perfusion decreased to 130 (27) ml/min/100 g (P < 0.05), with variable responses in terms of perfusion reserve. Pacing caused a redistribution of myocardial stress perfusion and perfusion reserve. The coefficient of regional variation of myocardial stress perfusion decreased from 19.7 (7.0)% to 14.6 (3.9)% during pacing (12.9 (3.8)% in controls, P < 0.01). The coefficient of regional variation of perfusion reserve decreased from 16.7 (6.6)% to 11.4 (2.6)% during pacing (9.8 (4.1)% in controls, P < 0.01). CONCLUSIONS: Pacing caused a decrease of resting left ventricular myocardial blood flow and blood flow during pharmacologically induced coronary vasodilatation. Although global perfusion reserve remained unchanged, myocardial perfusion reserve became more homogeneously distributed.

In atrial fibrillation, exercise capacity is often reduced. This is usually ascribed to a decreased cardiac output as coin compared with sinus rhythm. Very few studies, however, have focused oil changes in the peripheral blood flow during atrial fibrillation as a potential mechanism for exercise limitation. The aim of the present study was to determine the effect of conversion of atrial fibrillation to sinus rhythm on peripheral blood flow. Calf blood flow, using an electrocardiogram-triggered venous occlusion plethysmograph, and peak oxygen consumption (peak VO2), using treadmill exercise testing, were studied in 28 patients with chronic atrial fibrillation eligible for electrical cardioversion. Measurements were performed before cardioversion, and repeated 1 day and 1 month thereafter. Calf blood flow at rest, maximal calf blood flow, and minimal calf vascular resistance during the hyperaemic response immediately following 700 J of calf exercise were determined plethysmographically. One day and 1 month after cardioversion, 23 and 14 patients were still in sinus rhythm, respectively. In patients who still had sinus rhythm after 1 month, maximal calf blood Bow increased from 37.7 +/- 12 to 40.0 +/- 13 ml. 100 ml(-1 min-1) (P

Safety and efficacy of propafenone and disopyramide for long-term maintenance of sinus rhythm after electrical cardioversion was studied in 56 patients with chronic atrial fibrillation (median arrhythmia duration, 5 months). After cardioversion, patients were randomly assigned to receive double-blind propafenone 300 mg tid (25 patients) or disopyramide 250 mg tid (31 patients). Downward dose adjustment was allowed in case of intolerable side effects. The endpoints were arrhythmia recurrence; and side effects not amenable to dose reduction. For patients randomized to propafenone (mean dose, 878 +/- 65 mg/day), 66% [95% confidence interval [(CI) 46-85%] and 55% (95% CI, 34-76%) remained in sinus rhythm at 3 and 6 months, respectively (Kaplan-Meier method). Similar figures were found with disopyramide (mean dose, 704 +/- 81 mg/day): 71% (95% CI, 54-87%) and 67% (95% CI, 50-84%) at 3 and 6 months, respectively (p = NS). In the patients with a relapse of atrial fibrillation, the ventricular rate while still using the prophylactic agents did not increase significantly compared with precardioversion. However, one patient on disopyramide had an excessively high relapse heart rate (170 vs. 100 beats/min). Side effects were more frequent on disopyramide. Side effects necessitating drug discontinuation occurred in 12 patients: 4 patients (16%) on propafenone and 8 (26%) on disopyramide. Severe adverse effects occurred in two patients, who developed heart failure while on disopyramide. There were no proarrhythmic events or deaths. Thus, propafenone and disopyramide are equally effective for maintaining sinus rhythm after cardioversion of atrial fibrillation. Propafenone is, however, better tolerated than disopyramide, which may cause heart failure.

Ventricular arrhythmias remain a major problem, in particular in patients with left ventricular dysfunction or heart failure. In this group of patients, Class I drugs were shown to be ineffective, and they even increased mortality during chronic treatment. New antiarrhythmic agents should preferably not only have pure antiarrhythmic effects, but should also be free from adverse autonomic properties. In the present study, the electrophysiological, rate dependent and autonomic effects of intravenously administered almokalant, a new Class III antiarrhythmic drug, were investigated in nine pigs surviving a myocardial infarction. The ventricular effective refractory period (VERP) increased after almokalant (loading dose: 0.05 mu mol . kg(-1). min(-2), continuous infusion: 0.0025 mu mol . kg(-1). min(-1)) from 292 +/- 25 to 308 +/- 13 ms (pacing cycle length [PCL] 500 ms + 1 extrasystole [ES], from 249 +/- 19 to 261 +/- 16 ms (PCL 400 ms +1ES), and from 209 +/- 1 8 to 219 +/- 18 ms (PCL 300 ms +1ES). The VERPs increased most after three ES at PCL 400 ms: from 167 +/- 27 to 186 +/- 29 ms IP

The electrophysiologic effects of intravenously administered almokalant, a new class III antiarrhythmic drug, in 7 isoflurane-anesthetized pigs after low and high dose were investigated. Low-dose almokalant included bolus infusion of 0.05 mumol/kg/min for 5 min followed by a continuous infusion of 0.0025 mumol/kg/min for 40 min. Thereafter, a high dose of 0.2 mumol/kg/min for 5 min and 0.01 mumol/kg/min for 40 min was given. PR, QRS, AH, and HV intervals did not change during almokalant administration. The QT interval increased dose dependently from 337 +/- 17 to 442 +/- 20 ms at high dose (p < 0.05). Atrial refractory periods (AERP) were prolonged dose dependently at a 500-ms pacing cycle length from 178 +/- 15 at baseline to 227 +/- 27 and 253 +/- 23 ms during low- and high-dose almokalant infusion, respectively. For pacing cycle lengths of 400 and 300 ms, these values were 180 +/- 11, 207 +/- 25, and 259 +/- 34 and 157 +/- 12, 193 +/- 21, and 234 +/- 28 ms, respectively. At a pacing cycle length of 500 ms, mean ventricular effective refractory period (VERP) was 270 +/- 25 ms as compared with 306 +/- 24 and 337 +/- 17 during low and high dose, respectively. A similar pattern of VERP changes during both low- and high-dose infusion was noted at the shorter pacing cycle lengths, with an increase from 240 +/- 23 to 274 +/- 22 and 279 +/- 24 ms during a 400-ms cycle length and from 210 +/- 17 to 235 +/- 19 and 234 +/- 21 ms during a 300-ms cycle length. The ratio of the VERP and ventricular monophasic action potential duration (VAPD) did not change significantly. The Wenckebach cycle length increased by 36 +/- 36 and 83 +/- 37 ms with low- and high-dose almokalant infusion, respectively. The percent increase of AERP at pacing cycle lengths of 500, 400, and 300 ms during high-dose almokalant was 42, 44, and 49%, respectively; these increases for VERP were 25, 16, and 11%, respectively. In conclusion, prolongation of refractoriness by almokalant was more pronounced at the atrial than the ventricular level. Prolongation of refractoriness was maintained at short pacing cycle lengths especially in the atrium, indicating absence of reverse-use dependence of almokalant in the porcine heart. The marked atrial effects, paralleled by atrioventricular conduction slowing, and the absence of reverse use-dependence all contribute to the feasibility of use of almokalant, in particular in the treatment of supraventricular tachyarrhythmias.

Background Rising costs of health care, partly as a result of costly therapeutic innovations, are of concern to both the medical profession and healthcare authorities. The implantable cardioverter-defibrillator (ICD) is still not remunerated by Dutch healthcare insurers. The aim of this study was to evaluate the cost-effectiveness of early implantation of the ICD in postinfarct sudden death survivors. Methods and Results Sixty consecutive postinfarct survivors of cardiac arrest caused by ventricular tachycardia or fibrillation were randomly assigned either ICD as first choice (n=29) or a tiered therapy starting with antiarrhythmic drugs and guided by electrophysiological (EP) testing (n=31). Median follow-up was 729 days (range, 3 to 1675 days). Fifteen patients died, 4 in the early ICD group and 11 in the EP-guided strategy group ( P =.07). For quantitative assessment, the cost-effectiveness ratio was calculated for both groups and expressed as median total costs per patient per day alive. Because effectiveness aspects other than mortality are not incorporated in this ratio, other factors related to quality of life were used as qualitative measures of cost-effectiveness. The cost-effectiveness ratios were $63 and $94 for the early ICD and EP-guided strategy groups, respectively, per patient per day alive. This amounts to a net cost-effectiveness of $11 315 per patient per year alive saved by early ICD implantation. Costs in the early ICD group were higher only during the first 3 months of follow-up, but as a result of the high proportion of therapy changes, including arrhythmia surgery and late ICD implantation, costs in the EP-guided strategy group became higher after that. Patients discharged with antiarrhythmic drugs as sole therapy had the lowest total costs. This subset, however, showed extremely high mortality, resulting in a poor cost-effectiveness ratio ($196 per day). Invasive therapies and hospitalization were the major contributors to costs. If quality-of-life measures are taken into account, the cost-effectiveness of early ICD implantation was even more favorable. Recurrent cardiac arrest and cardiac transplantation occurred in the EP-guided strategy group only, whereas exercise tolerance, total hospitalization duration, number of invasive procedures, and antiarrhythmic therapy changes were significantly in favor of early ICD implantation. Conclusions In terms of cost-effectiveness, early ICD implantation is superior to the EP-guided therapeutic strategy in postinfarct sudden death survivors.

Analysis of Heart Rate Variability is a non-invasive quantitative tool to study the influence of the autonomic nervous system on the heart. Rapid variations in heart rate, related to breathing are primarily mediated by the vagal limb of the autonomic nervous system. The resulting variations in heart rate are usually referred to as respiratory sinus arrhythmia. Metronome breathing (MB) is often advocated to assess more accurately vagal control. However, the additional value of MB over SB has never been established. The authors studied the effect of MB (0.25 Hz) on HRV variables in 12 healthy male subjects under stable conditions using pharmacological autonomic blockade. During MB several variables showed a lower absolute value, however a strong correlation existed between variables computed during spontaneous breathing (SB) and MB. MB offers some, but no important advantages over spontaneous breathing.