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BACKGROUND: Whether atrial fibrillation (AF) pattern or timing of AF therapy modifies the effectiveness of early rhythm control (ERC) is not known. OBJECTIVES: This study sought to compare clinical characteristics and outcomes in patients presenting with different AF patterns on ERC vs usual care. METHODS: The effects of ERC were compared in first-diagnosed AF (FDAF), paroxysmal AF (paroxAF), and persistent AF (persAF) in this prespecified analysis of the EAST-AFNET 4 (Early treatment of atrial fibrillation for stroke prevention) trial. Associations between AF pattern and primary outcomes (first primary outcome: cardiovascular death, stroke, and hospitalization for heart failure and acute coronary syndrome; second primary outcome: nights spent in hospital per year) were compared over a mean follow-up of 5.1 years. Changes in health-related quality of life were assessed by the EQ-5D. RESULTS: FDAF patients (n = 1,048, enrolled 7 days after diagnosing AF) were slightly older (71 years of age, 48.0% female) than patients with paroxAF (n = 994, 70 years of age, 50.0% female) and persAF (n = 743, 70 years of age, 38.0% female). ERC reduced the primary outcome in all 3 AF patterns. Hospitalizations for acute coronary syndrome were highest in FDAF (incidence rate ratio [IRR]: 1.50; 95% CI: 0.83-2.69; P for interaction = 0.032) compared with paroxAF (IRR: 0.64; 95% CI: 0.32-1.25) and persAF (IRR: 0.50; 95% CI: 0.25-1.00). FDAF patients spent more nights in hospital (IRR: 1.38; 95% CI: 1.12-1.70; P for interaction = 0.004) than paroxAF (IRR: 0.84; 95% CI: 0.67-1.03), and persAF (IRR: 1.02; 95% CI: 0.80-1.30) patients. ERC improved health-related quality of life (EQ-5D score) in patients with paroxAF and persAF but not in patients with FDAF (P = 0.019). CONCLUSIONS: ERC reduces the first primary composite outcome in all AF patterns. Patients with FDAF are at high risk for hospitalization and acute coronary syndrome, particularly on ERC. (Early treatment of atrial fibrillation for stroke prevention trial; ISRCTN04708680; Early Treatment of Atrial Fibrillation for Stroke Prevention Trial [EAST]; NCT01288352; Early treatment of Atrial fibrillation for Stroke prevention Trial [EAST]; EudraCT2010-021258-20).

BACKGROUND: Oral and intravenous flecainide is recommended for cardioversion of atrial fibrillation. In this open-label, dose-escalation study, the feasibility of delivering flecainide via oral inhalation (flecainide acetate inhalation solution) for acute conversion was evaluated. We hypothesized that flecainide delivered by oral inhalation would quickly reach plasma concentrations sufficient to restore sinus rhythm in patients with recent-onset atrial fibrillation. METHODS: Patients (n=101) with symptomatic atrial fibrillation (for ≤48 hours) self administered flecainide acetate inhalation solution using a nebulizer (30 mg [n=10], 60 mg [n=22], 90 mg [n=21], 120 mg [n=19], and 120 mg in a formulation containing saccharin [n=29]). Electrocardiograms and flecainide plasma concentrations were obtained, cardiac rhythm using 4-hour Holter was monitored, and adverse events were recorded. RESULTS: Conversion rates increased with dose and with the maximum plasma concentrations of flecainide. At the highest dose, 48% of patients converted to sinus rhythm within 90 minutes from the start of inhalation. Among patients who achieved a maximum plasma concentration >200 ng/mL, the conversion rate within 90 minutes was 50%; for those who achieved a maximum plasma concentration

of the progress in arrhythmias in 2020. RACE4 and ALL-IN indicated that integrated nurse-led care improves outcomes in AF patients.3,4 The same was reported for early rhythm control therapy15 and cryoablation as initial AF treatment.25,26 Subcutaneous ICD was non-inferior to classical transvenous ICD therapy in PRAETORIAN.54 One mechanistic study showed that autoantibodies against misexpressed actin, keratin, and connexin-43 proteins create a blood-borne biomarker profile enhancing diagnosis of Brugada syndrome.50 Another mechanistic study indicated that transseptal LV pacing yields similar improvement in contractility as His bundle pacing whilst being more easy to execute.44 In PRE-DETERMINE a simple-to-use ECG risk score improved risk prediction in patients with ischemic heart disease possibly enhancing appropriate ICD therapy in high risk patients.58.

BACKGROUND: Adenosine can be used to reveal dormant pulmonary vein (PV) conduction after PV isolation (PVI). This study presents a subanalysis of real-world 1-year follow-up data from the ESC-EHRA EORP Atrial Fibrillation (AF) Ablation Long-Term registry to analyze the usage of adenosine during PVI treatment in terms of rhythm outcome and safety. METHODS: The registry consists of 104 participating centers in 27 countries within the European Society of Cardiology. The registry data was split into an adenosine group (AG) and no-adenosine group (NAG). Procedure characteristics and patient outcome were compared. RESULTS: Adenosine was administered in 10.8% of the 3591 PVI patients included in the registry. Spain, the Netherlands, and Italy included the majority of adenosine cases (48.8%). Adenosine was applied more often in combination with open irrigation radiofrequency (RF) energy (74.7%) and less often in combination with nonirrigated RF energy (1.6%). After 1 year, a higher percentage of the AG was free from AF compared with the NAG (68.9% vs 59.1%, p < 0.001). Adenosine was associated with better rhythm outcome in RF ablation procedures, but not in cryo-ablation procedures (freedom from AF: RF: AG: 70.9%, NAG: 58.1%, p < 0.001, cryo: AG: 63.9%, NAG: 63.8%, p = 0.991). CONCLUSIONS: The use of adenosine was associated with a better rhythm outcome after 1 year follow-up and seems more useful in patients treated with RF energy compared with patients treated with cryo energy. Given the improved rhythm outcome at 1-year follow-up, it seems reasonable to encourage the use of adenosine during RF AF ablation.

BACKGROUND: Previous research showed a significant difference in the presence of subclinical coronary artery disease (CAD) on cardiac CT angiography (CTA) between patients with idiopathic paroxysmal atrial fibrillation (iAF) versus a matched sinus rhythm population (iSR). Here we present 5-year follow-up data and the consequences of subclinical CAD on baseline CTA on the development of cardiovascular disease in iAF. METHODS: In 99 iAF patients (who underwent CTA as part of work-up for pulmonary vein isolation) and 221 matched iSR controls (who underwent CTA for CAD assessment), the incidence of hypertension, diabetes and major cardiovascular events (MACCE) during follow-up was obtained. Multivariable Cox regression analysis was used to reveal predictors of incident cardiovascular disease in the iAF group. RESULTS: During a follow-up of 68±11 months, over one third of patients developed cardiovascular disease, with no difference between iAF and iSR (log-rank p=0.56), and comparable low rates of MACCE (4.0% vs 5.0%,p=0.71). Within the iAF group, age (HR1.12(1.03–1.20);p=0.006), left atrial diameter (HR1.16(1.03–1.31);p=0.01), Segment Involvement Score (total number of coronary segments with atherosclerotic plaque; HR1.43(1.09–1.89);p=0.01) and the number of calcified plaques on CTA (HR0.53(0.30–0.92);p=0.01) were independent predictors of incident cardiovascular disease. CONCLUSIONS: Subclinical coronary disease on CTA may be useful to identify the subset of patients with iAF that harbour concealed cardiovascular risk factors and need intensive clinical follow-up to ensure timely initiation of appropriate therapy once CV disease develops, including anticoagulation and vascular prophylactic therapy.

Quantification of myocardial beta-adrenoceptor density (B-max) is of interest in cardiac diseases in which altered function of the sympathetic nervous system is thought to play a pathophysiological role. PET provides an unrivaled means of taking regional measurements of cardiac microcirculatory function, tissue metabolism and autonomic nervous system activity. Measurements in small regional areas may be biased because of increased noise levels. This study examined the parametric polar map approach for the regional quantification of B-max. Methods: Dynamic PE-T with parametric polar map imaging was performed in 10 healthy volunteers and 4 patients with hypertrophic cardiomyopathy using (S)-[C-11]-(4-(3-tertiarybutylamino-2-hydroxypropoxy)-benzidimazole-2)-o n hydrochloride (CGP)-12177 and a double-injection protocol. Time-activity curves were corrected for partial volume, spill-over and wall motion effects. The mean B-max of the left ventricle was calculated in two ways. First, the average time-activity curve of all segments, having the highest achievable signal-to-noise ratio, was used to calculate B-max(mTAC) (the myocardial beta-adrenoceptor density of the left ventricle calculated using the average time-activity curve). The bias in B-max(mTAC) introduced by noise is minimal. Second, an estimate of whole-heart receptor density was calculated using the polar map method by averaging the values of B-max obtained for 576 individual segments. In these calculations, three different filters (3 x 5, 3 x 9 and 3 x 13 segments) were used to smooth the time-activity curves before calculating B-max. Mean values of whole-left-ventricular receptor density obtained by averaging regional values using the different filters (B-max(PMF1/2/3)) were compared with B-max(mTAC) to assess bias introduced by the polar map approach. Segments with a calculated B-max outside the range 0.1-50 pmol/g were considered unreliable and were excluded from the analysis. Results: The differences between the two methods of calculating B-max were small (7.8%, 4.8% and 3.2%, with the three filters, respectively). Reliable results were obtained in >95% of the segments and in 9 volunteers and all 4 patients. Conclusion: When using PET for the quantification of beta-adrenoceptor density, the regional variation in B-max can be reliably assessed using the parametric polar map approach.

Objectives The purpose of this study was to assess whether management of heart failure (HF) guided by an individualized N-terminal pro-B-type natriuretic peptide (NT-proBNP) target would lead to improved outcome compared with HF management guided by clinical assessment alone. Background Natriuretic peptides may be attractive biomarkers to guide management of heart failure (HF) and help select patients in need of more aggressive therapy. The PRIMA (Can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?) study is, to our knowledge, the first large, prospective randomized study to address whether management of HF guided by an individualized target NT-proBNP level improves outcome. Methods A total of 345 patients hospitalized for decompensated, symptomatic HF with elevated NT-proBNP levels at admission were included. After discharge, patients were randomized to either clinically-guided outpatient management (n = 171), or management guided by an individually set NT-proBNP (n = 174) defined by the lowest level at discharge or 2 weeks thereafter. The primary end point was defined as number of days alive outside the hospital after index admission. Results HF management guided by this individualized NT-proBNP target increased the use of HF medication (p = 0.006), and 64% of HF-related events were preceded by an increase in NT-proBNP. Nevertheless, HF management guided by this individualized NT-proBNP target did not significantly improve the primary end point (685 vs. 664 days, p = 0.49), nor did it significantly improve any of the secondary end points. In the NT-proBNP-guided group mortality was lower, as 46 patients died (26.5%) versus 57 (33.3%) in the clinically-guided group, but this was not statistically significant (p = 0.206). Conclusions Serial NT-proBNP measurement and targeting to an individual NT-proBNP value did result in advanced detection of HF-related events and importantly influenced HF-therapy, but failed to provide significant clinical improvement in terms of mortality and morbidity. (Effect of NT-proBNP Guided Treatment of Chronic Heart Failure [PRIMA]; NCT00149422) (J Am Coll Cardiol 2010;56:2090-100) (C) 2010 by the American College of Cardiology Foundation

Background Myocardial stress and strain are considered primary mechanical stimuli for hypertrophic remodeling. Their values and significance in the intact beating heart during chronic overload remain poorly characterized. Methods and results Left-ventricular (LV) dimensions (echocardiography) and pressure ( invasive) were simultaneously recorded in anesthetized dogs at sinus rhythm (SR), acute and 1, 2, 6, 12 weeks of atrioventricular block (AVB), leading to structural, electrical and contractile remodeling. Mechanical load of the myocardium was quantified as myofiber stress (sigma(f)), being force along myofiber orientation per cross-sectional area, and natural myofiber strain (e(f)), being change in natural logarithm of myofiber length ( l) divided by its reference length: e(f) = ln( l/l(ref)). Time courses of sigma(f) and e(f) were calculated from LV pressure and dimensions, using a validated mathematical model of cardiac mechanics. End-diastolic sigma(f) increased from 2.0 +/- 0.1 kPa at SR to 3.4 +/- 0.3 kPa at acute AVB, remaining elevated for > 6 weeks. Systolic sigma(f) was not affected by AVB. Ejection strain rose instantly upon AVB, reaching a maximum at 2 weeks: 0.24 +/- 0.02 vs. 0.10 +/- 0.01 at SR. The increase of myofiber stroke work ( sigma(f)-e(f) loop area) from 3.1 +/- 0.3 at SR to 6.0 +/- 0.5 kJ/m(3)/ beat at 1 week AVB was attributed mainly to an increase of strain during ejection. Stroke work and ejection strain remained elevated up to 12 weeks. The rate of LV-mass increase was maximal (2.2 +/- 0.4 g/day) at 1 week AVB. Conclusions Serial mechanical phenotyping is feasible in the intact anesthetized dog with chronic ventricular overload. Our new approach yields values of mechanical load that are comparable to those found in isolated myocardium by others. In chronic AVB, both end-diastolic myofiber stress and ejection strain are increased. Early increases of both parameters coincide with peak hypertrophic growth, suggesting their important role for mechanotransduction. Peak systolic sigma f is likely not important for hypertrophy in this model, since it does not change throughout the experiment.

Aim Differential drug treatment guided by the underlying heart disease 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 hypertension 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 successful 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 recurrences peaked on day 2-3 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 regression analysis demonstrated that beta-blockade was the only statistically significant parameter predicting sinus rhythm at 1 month (OR 0.40, 95% CI 0.19-0.86, P = 0.02). Conclusions Compared with lone AF patients, patients in the setting of hypertension maintain sinus rhythm much better after cardioversion when treated with a beta-blocker. Beta-blockade protects, in particular, against the early subacute recurrences. These findings underscore the importance of a differential approach towards drug prevention of post-cardioversion recurrences depending on the underlying heart disease. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.

Background: Congestive heart failure (CHF) is characterized by neurohormonal activation, including increased plasma concentrations of atrial natriuretic peptide (ANP) and N-terminal ANP (N-ANP). Onset of atrial fibrillation (AF) further increases these peptides, but it may be hypothesized that concentrations decrease during longstanding AF due to inherent atrial degeneration. Aim: We sought to investigate the relation between neurohormonal activation in patients with CHF and the duration of concomitant AF Methods: The study group comprised 60 patients (age 70+/-8 years) with advanced CHF due to left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) 0.25 ANP and N-ANP increased along with the duration of AF, whereas in patients with LVEFless than or equal to0.25 an inverse relation between ANP (P=0.02) and N-ANP (P=0.04) and the duration of AF was present, longer-standing AF being associated with lower concentrations. Conclusion: In patients with advanced CHF with low LVEF plasma ANP and N-ANP concentrations decrease during longstanding AF. This finding agrees with the concept that longstanding AF leads to impaired ability of the atria to produce these neurohormones due to inherent degenerative changes. (C) 2002 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.

Objective: Atrial fibrillation (AF) is accompanied by electrical. structural and ion-channel protein remodeling. We tested if proteolysis by calpain and proteasome is activated during AF. and studied the relation with the remodeling processes. Methods: Right atrial appendages were obtained from patients with paroxysmal (n = 7) or persistent (n = 10) lone AF and compared to controls (n = 10) in sinus rhythm undergoing coronary artery bypass grafting (CABG). Proteolysis was measured using Suc-Leu-Leu-Val-Tyr-7-amino-4-methyl-coumarin. Protein expression of calpain I and 11 was assessed by Western-blot and calpain I localization by immunohistochemistry. Structural changes were quantified by counting atrial myocytes with contraction bands or hibernation. Results: Calpain activity was significantly increased in paroxysmal AF (2-fold, P

Background: Endothelial dysfunction is useful in predicting future cardiovascular disease. At present several tests are available to test endothelial function: coronary diameter response to acetylcholine, forearm bloodflow (FBF) response to acetylcholine, and brachial artery flow-mediated dilative (FMD) response to postischemic hyperemia. This study aimed to compare the three most frequently reported endothelial function tests. Methods: Twenty-eight patients (19 males and nine females, mean age 57 years) referred for diagnostic coronary angiography were considered for endothelial function measurement in the coronary artery as well as in the forearm by FBF and FMD. Results: Acetylcholine decreased the mean coronary diameter by 7.4% (SD 6.3%) and increased the mean FBF by 230% (SD 152%). Hyperemia increased the mean brachial diameter by 6.7% (SD 4.8%). The effect of acetylcholine on forearm resistance vessels was significantly related to the effect of acetylcholine on the coronary conduit vessels (P=0.039). Nonetheless, FMD was not related to FBF nor to the coronary response. Conclusion: In patients with mild coronary endothelial dysfunction, forearm vasoreactivity is related to the coronary response, provided that the same stimulus is used.

We wondered whether, in an elderly hypertensive population in a primary prevention setting, free from diabetes mellitus and clinical atherosclerosis, differences between end organ damage and microalbuminuria (MA) could be found using a lower level of urinary albumin excretion than that of classically defined MA. From a population survey of 173 previously untreated hypertensive patients (4x blood pressure systolic greater than or equal to 160 and less than or equal to220 mmHg, and/or diastolic greater than or equal to95 and less than or equal to115 mmHg), mean age 67 +/- 4 years, were screened for MA (defined as albumin excretion between 20 and 300 mg/24 h). End organ damage was determined by B-mode ultrasound scanning of carotid and femoral arteries and echocardiography. Out of 173 hypertensives, 14 showed MA (8%,). These hypertensives had a significantly higher intima media thickness (IMT; 1.01 +/- 0.21 vs 0.88 +/- 0.6 mm, p

Background: Paroxysmal atrial fibrillation is associated with various symptoms, including dizziness, which presumably reflects hemodynamic deterioration. Given the importance of the autonomic nervous system in mitigating the hemodynamic effect of atrial fibrillation, we hypothesized that autonomic function would be predictive of the severity of dizziness. Methods: The study group comprised 73 patients with paroxysmal atrial fibrillation (mean age 54.1 years, 51 males). Forty-three (59%) patients had lone atrial fibrillation. Mean ventricular rate during atrial fibrillation was 99+/-16 beats/min. On average, patients had a 3-year history of one paroxysm per week lasting 2 h. Autonomic function was assessed using autonomic function tests, including noninvasive measurement of baroreflex sensitivity. Head up tilting was used to test vasovagal reactivity. Severity of dizziness at onset of atrial fibrillation was quantified by the patients using a five-point scale (1=none; 2=light; 3=mild; 4=moderate; and 5=severe). Multivariate analysis was performed to identify the independent predictors of the severity of dizziness. Results: Mean severity of dizziness was 3.36+/-1.65. Multivariate predictors of moderate-to-severe dizziness as opposed to none-to-mild dizziness were a low 30-15 ratio after standing up and low baroreflex sensitivity. Though syncope was never reported nine patients showed a full vasovagal response during head up tilting. Conclusions: It is concluded that dizziness in patients with "treated" atrial fibrillation in the setting of none to mild structural heart disease is predicted by impaired autonomic function. Vasovagal reactivity appears not to be involved in this connection. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

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

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

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.

We demonstrated that in a large nondiabetic population, a graded continuous relation was present between the level of urinary albumin excretion and ischemic electrocardiographic abnormalities, without an apparent threshold. These data suggest that the level of urinary albumin excretion can be used to establish cardiovascular risk in the population at large.

Aim: Autonomic impairment is related to the incidence of sudden death in chronic heart failure (CHF). Our objective was to study autonomic profiles in patients with mild CHF due to coronary artery disease, and to investigate the value of add-on P-blockade. Methods and results: Measures of autonomic function (plasma norepinephrine, heart rate [HR] variability, autonomic function testing), and exercise capacity, were compared between 24 patients with mild CHF, and 24 healthy controls. In this mechanistic study, we assessed the effect of 26 weeks metoprolol treatment in a double-blind, randomized, placebo-controlled design. All patients received metoprolol sustained release (200 mg; n = 12) or placebo (n = 12). Assessments were made at baseline and after 10 and 26 weeks' treatment. At baseline, norepinephrine levels were elevated, while HR variability parameters were decreased in patients vs. controls (both P

Aim To assess the value of microalbuminuria as an indicator of increased cardiovascular risk in a non-diabetic population. Methods and Results 7579 non-diabetic subjects were studied with ages ranging from 28 to 75 years selected from a population based cohort. Using computerized Minnesota coding, ischaemic electrocardiographic abnormalities were divided into three categories: infarct patterns, major ischaemia. and minor ischaemia. Urinary albumin excretion was measured as the mean of two 24-h urine collections. Cardiovascular risk indicators were defined as an age above 60 Fears, male sex, hypertension, hypercholesterolaemia, smoking, obesity and a positive cardiovascular family history. Microalbuminuria was associated with age, sea, blood pressure, serum cholesterol, serum glucose, body mass index and all three categories of electrocardiographic abnormalities. In a multivariate model, adjusted for established cardiovascular risk indicators, microalbuminuria was independently associated with infarct patterns (OR [95% CI] 1.61 [1.12-2.32]), major ischaemia (OR 1.43 [1.08-1.91]) and minor ischaemia (OR 1.32 [1.03-1.68]). Conclusions The independent association between microalbuminuria and ischaemic electrocardiographic abnormalities suggests that microalbuminuria has additional value to conventional risk indicators in predicting cardiovascular disease in non-diabetics. Assessment of microalbuminuria could be an instrument to identify those at an increased risk for coronary vascular disease in an early stage. (C) 2000 The European Society of Cardiology.

OBJECTIVES: We sought to investigate the effect of angiotensin-converting enzyme (ACE) inhibition BACKGROUND: The ACE inhibitors reduce mortality after MI. Attenuation of LV dilation has been suggested as an important mechanism. METHODS: The data of 845 patients with three-month echocardiographic follow-up after MI were combined from three randomized, double-blind, placebo-controlled studies. The criteria for these studies included: 1) thrombolytic therapy; 2) ACE inhibition within 6 to 9 h; and 3) evaluation of LV dilation as the primary objective. RESULTS: The ACE inhibitor was started 3.2 +/- 1.7 h after the patients' first (mainly, 85%) anterior MI. After three months, LV dilation was not significantly attenuated by very early treatment with an ACE inhibitor. The diastolic volume index was attenuated by 0.5 ml/m(2) (95% confidence interval [CI] -1.5 to 2.5, p = 0.61), and the systolic volume index by 0.5 ml/m2 (95% CI -1.0 to 1.9, p = 0.50). Subgroup analysis demonstrated that LV dilation was significantly attenuated by ACE inhibitor treatment for patients in whom reperfusion failed. In contrast, LV dilation was almost unaffected by ACE inhibitor treatment in successfully reperfused patients. CONCLUSIONS: We could not demonstrate attenuation of LV dilation in patients receiving thrombolysis by ACE inhibitor treatment within 6 to 9 h after MI. We speculate that very early treatment with an ACE inhibitor has a beneficial effect on LV remodeling only in patients in whom reperfusion failed. Other mechanisms may be responsible for the beneficial effects of ACE inhibitors in successfully reperfused patients after MI. (C) 2000 by the American College of Cardiology.

This study describes the rationale, design, and baseline characteristics of a trial to determine whether treatment with fosinopril 20 mg/day and/or pravastatin 40 mg/day will prevent cardiovascular and renal disease in nonhypertensive (RR 10 mg/L once in an early morning spot urine and 15 to 300 mg/24-hour at least once in two 24-hour urine collections). The Prevention of REnal and Vascular ENdstage Disease Intervention Trial is a single-center, double-blind, randomized, placebo-controlled trial with a 2 x 2 factorial design. The 864 randomized subjects will be monitored for a minimum of 4 years and a maximum of 5 years. The primary efficacy parameter is defined as the combined incidence of all-cause mortality or hospital admission for documented (1) nonfatal myocardial infarction, (2) myocardial ischemia, (3) heart failure, (4) peripheral vascular disease, (5) cerebrovascular accident and/or (6) end-stage renal disease. (C) 2000 by Excerpta Medica, Inc.