Performance of seven ECG interpretation programs in identifying arrhythmia and acute cardiovascular syndrome.

BACKGROUND: No direct comparison of current electrocardiogram (ECG) interpretation programs exists. OBJECTIVE: Assess the accuracy of ECG interpretation programs in detecting abnormal rhythms and flagging for priority review records with alterations secondary to acute coronary syndrome (ACS). METHODS: More than 2,000 digital ECGs from hospitals and databases in Europe, USA, and Australia, were obtained from consecutive adult and pediatric patients and converted to 10 s analog samples that were replayed on seven electrocardiographs and classified by the manufacturers' interpretation programs. We assessed ability to distinguish sinus rhythm from non-sinus rhythm, identify atrial fibrillation/flutter and other abnormal rhythms, and accuracy in flagging results for priority review. If all seven programs' interpretation statements did not agree, cases were reviewed by experienced cardiologists. RESULTS: All programs could distinguish well between sinus and non-sinus rhythms and could identify atrial fibrillation/flutter or other abnormal rhythms. However, false-positive rates varied from 2.1% to 5.5% for non-sinus rhythm, from 0.7% to 4.4% for atrial fibrillation/flutter, and from 1.5% to 3.0% for other abnormal rhythms. False-negative rates varied from 12.0% to 7.5%, 9.9% to 2.7%, and 55.9% to 30.5%, respectively. Flagging of ACS varied by a factor of 2.5 between programs. Physicians flagged more ECGs for prompt review, but also showed variance of around a factor of 2. False-negative values differed between programs by a factor of 2 but was high for all (>50%). Agreement between programs and majority reviewer decisions was 46-62%. CONCLUSIONS: Automatic interpretations of rhythms and ACS differ between programs. Healthcare institutions should not rely on ECG software "critical result" flags alone to decide the ACS workflow.

Cardiac resynchronization therapy: a comparison among left ventricular bipolar, quadripolar and active fixation leads.

We evaluated the performance of 3 different left ventricular leads (LV) for resynchronization therapy: bipolar (BL), quadripolar (QL) and active fixation leads (AFL). We enrolled 290 consecutive CRTD candidates implanted with BL (n = 136) or QL (n = 97) or AFL (n = 57). Over a minimum 10 months follow-up, we assessed: (a) composite technical endpoint (TE) (phrenic nerve stimulation at 8 V@0.4 ms, safety margin between myocardial and phrenic threshold <2V, LV dislodgement and failure to achieve the target pacing site), (b) composite clinical endpoint (CE) (death, hospitalization for heart failure, heart transplantation, lead extraction for infection), (c) reverse remodeling (RR) (reduction of end systolic volume >15%). Baseline characteristics of the 3 groups were similar. At follow-up the incidence of TE was 36.3%, 14.3% and 19.9% in BL, AFL and QL, respectively (p < 0.01). Moreover, the incidence of RR was 56%, 64% and 68% in BL, AFL and QL respectively (p = 0.02). There were no significant differences in CE (p = 0.380). On a multivariable analysis, "non-BL leads" was the single predictor of an improved clinical outcome. QL and AFL are superior to conventional BL by enhancing pacing of the target site: AFL through prevention of lead dislodgement while QL through improved management of phrenic nerve stimulation.

AF burden is important - fact or fiction?

Asymptomatic atrial fibrillation (AF) is common and in view of its prognostic impact (the same as of clinically overt AF) knowledge of the overall AF burden (defined as the amount of time spent in AF) appears to be important, both for scientific and clinical reasons. Data collected on more than 12,000 patients indicate that cardiac implantable electrical devices (CIEDs) are validated tools for measuring AF burden and that AF burden is associated with an increased risk of stroke. A maximum daily AF burden of ≥ 1 h carries important negative prognostic implications and may be a clinically relevant parameter for improving risk stratification for stroke. Decision-making should primarily consider the context in which asymptomatic, subclinical arrhythmias are detected (i.e. primary or secondary prevention of stroke and systemic embolism) and the risk profile of every individual patient with regard to thromboembolic and haemorrhagic risk, as well as patient preferences and values. Continuous monitoring using CIEDs with extensive data storage capabilities allow in-depth study of the temporal relationship between AF and ischaemic stroke. The relationships between AF and stroke are complex. AF is certainly a risk factor for cardioembolic stroke, with a cause-effect relationship between the arrhythmia and a thromboembolic event, the latter being related to atrial thrombi. However, AF can also be a simple 'marker of risk', with a non-causal association between the arrhythmia and stroke, the latter being possibly related to atheroemboli from the aorta, the carotid arteries or from other sources.

Expenditure and value for money: the challenge of implantable cardioverter defibrillators.

Many technology-driven interventions entail considerable financial cost, raising affordability issues. The implantable cardioverter defibrillator (ICD) is a case of an effective primary prevention intervention with high initial costs that is capable of delivering long-term population benefits. At first glance, such interventions may provoke diffidence, if not active resistance, due to the financial burdens which inevitably accompany their widespread adoption. In this article, we review the available economic tools that can help address the ICD cost issue. We think awareness of such knowledge may facilitate dialogues between physicians, administrators and policymakers, and help foster rational decision-making.

Electrical cardioversion for persistent atrial fibrillation or atrial flutter in clinical practice: predictors of long-term outcome.

Despite the results of Atrial Fibrillation Follow-up Investigation of Rhythm Management and Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation trials, which favour a general shift in atrial fibrillation (AF) therapeutic approach towards control of ventricular rate, a strategy based on restoration of sinus rhythm could still play a role in selected patients at lower risk of AF recurrence. We explored possible predictors of relapses after external electrical cardioversion among patients with persistent AF or atrial flutter (AFL). We analysed the clinical characteristics and conventional echocardiographic parameters of patients with persistent AF/AFL enrolled in an institutional electrical cardioversion programme. Among 242 patients (AF/AFL, 195/47; mean age 62+/-13 years), sinus rhythm was restored in 215 (89%) and maintained in 73 (34%) at a follow-up of 930 days (median). No baseline clinical/echocardiographic variables predicted acute efficacy of cardioversion at logistic regression analysis. However, two variables predicted long-term AF/AFL recurrence among patients with successful cardioversion at multivariate Cox's proportional hazards analysis: (i) duration of arrhythmia>or=1 year (HR, 2.07; 95% CI, 1.29-3.33) and (ii) presence of previous cardioversion (HR, 1.67; 95% CI, 1.17-2.38). These variables also presented high-positive predictive values (72% and 80% respectively). Whereas the high acute efficacy of electrical cardioversion (approximately 90%) does not appear to be predictable, two simple clinical variables could help identify patients at higher risk of long-term AF/AFL recurrence after successful electrical cardioversion. We think there could be a case for initially attempting external electrical cardioversion to patients who have had AF/AFL for <1 year. In such patients, the chance of long-term success appears to be relatively high.

A comparison of acute phase proteins and traditional risk factors as markers of combined plaque and intima-media thickness and plaque density in carotid and femoral arteries.

OBJECTIVES: To test the hypothesis that some acute phase proteins may be better independent predictors of objective measures of arterial wall impairment than traditional risk factors. DESIGN: Cross-sectional study. MATERIALS AND METHODS: C-reactive protein (CRP), fibrinogen, C3 complement and traditional risk factors were measured in 288 men aged 55-64 years, randomly chosen from the local registry lists. By ultrasound assessment of the bifurcations of carotid and femoral arteries, maximum combined plaque/intima-media thickness (CPIMTmax) and mean plaque density (MPD, in a grey scale from 0 to 255) were also measured. RESULTS: In multivariate analysis only traditional risk factors remained associated with the overall CPIMTmax: smoking (r = 0.35, p < 0.0001), cholesterol (r = 0.23, p = 0.0001), age (r = 0.22, p = 0.0002), glucose (r = 0.18, p = 0.002) and systolic blood pressure (r = 0.13, p = 0.02). However, with regard to carotid disease only, fibrinogen was the strongest covariate of CPIMT (r = 0.18, p = 0.002). The overall MPD was independently associated with CRP (r = 0.25, p = 0.0008), physical activity (r = 0.19, p = 0.009), triglycerides (r = -0.18, p = 0.02) and body mass index (r = 0.15, p = 0.04). CRP was mainly associated with femoral MPD, while triglycerides were the major (inverse) covariate of carotid MPD. CONCLUSIONS: Traditional risk factors are the main determinants of CPIMTmax, although fibrinogen seems to play a role in carotids. CRP was associated with high density femoral plaques. Finally, no acute phase protein was independently associated with low density, potentially vulnerable, plaques.

[Implantable defibrillators and prevention of sudden death: clinical and economic implications in the light of the MADIT II study]. / Defibrillatori impiantabili e prevenzione della morte improvvisa: implicazioni cliniche ed economiche alla luce dello studio MADIT II.

The cardioverter-defibrillator is the most effective strategy to prevent sudden death in patients with previous episodes of ventricular tachyarrhythmia (secondary prevention of sudden death). In recent years the possibility of primary prevention of sudden death in selected groups of high risk patients has raised great interest. The MADIT II study highlighted the possibility of preventing sudden death in patients with coronary artery disease. According to this trial, identification of such patients can be performed by means of few clinical data and without expensive screenings (i.e. electrophysiological study). Indeed, patients with a previous myocardial infarction and low left ventricular ejection fraction (< 30%) may benefit from the implant of a cardioverter-defibrillator, with a reduction of the mortality risk by about 31% in the following two years. In the light of these data, implant of a cardioverter-defibrillator should be proposed in such patients, even if the problem of limited economic resources to meet the cost of the devices has to be considered even in the richest country of the world. Despite the positive scientific result, MADIT II has raised the problem of the effective possibility of adopting this therapeutic strategy in clinical practice and this question is still open. Strategies to reduce the theoretically high costs implicated by the MADIT II study include a reduction in the cost of defibrillators through dynamic market forces, the identification of subgroups at higher risk of sudden death, and the use of cheap defibrillators with limited diagnostic and therapeutic options. A long-term evaluation of the cost-effectiveness for western countries of these strategies is necessary to identify in which patient subgroups implant of a cardioverter-defibrillator is acceptable, i.e. cost-effective, in terms of primary prevention.

Nitroxyl anion exerts redox-sensitive positive cardiac inotropy in vivo by calcitonin gene-related peptide signaling.

Nitroxyl anion (NO(-)) is the one-electron reduction product of nitric oxide (NO( small middle dot)) and is enzymatically generated by NO synthase in vitro. The physiologic activity and mechanism of action of NO(-) in vivo remains unknown. The NO(-) generator Angeli's salt (AS, Na(2)N(2)O(3)) was administered to conscious chronically instrumented dogs, and pressure-dimension analysis was used to discriminate contractile from peripheral vascular responses. AS rapidly enhanced left ventricular contractility and concomitantly lowered cardiac preload volume and diastolic pressure (venodilation) without a change in arterial resistance. There were no associated changes in arterial or venous plasma cGMP. The inotropic response was similar despite reflex blockade with hexamethonium or volume reexpansion, indicating its independence from baroreflex stimulation. However, reflex activation did play a major role in the selective venodilation observed under basal conditions. These data contrasted with the pure NO donor diethylamine/NO, which induced a negligible inotropic response and a more balanced veno/arterial dilation. AS-induced positive inotropy, but not systemic vasodilatation, was highly redox-sensitive, being virtually inhibited by coinfusion of N-acetyl-l-cysteine. Cardiac inotropic signaling by NO(-) was mediated by calcitonin gene-related peptide (CGRP), as treatment with the selective CGRP-receptor antagonist CGRP(8-37) prevented this effect but not systemic vasodilation. Thus, NO(-) is a redox-sensitive positive inotrope with selective venodilator action, whose cardiac effects are mediated by CGRP-receptor stimulation. This fact is evidence linking NO(-) to redox-sensitive cardiac contractile modulation by nonadrenergic/noncholinergic peptide signaling. Given its cardiac and vascular properties, NO(-) may prove useful for the treatment of cardiovascular diseases characterized by cardiac depression and elevated venous filling pressures.

Relationship of serum C3 to fasting insulin, risk factors and previous ischaemic events in middle-aged men.

AIMS: Serum C3 is a powerful indicator of the risk of myocardial infarction, which correlates with body mass index, serum lipids and blood pressure. This study was performed to ascertain whether such correlations may be explained by an association of C3 with fasting insulin, and to assess comparatively the relationships of C3 and traditional risk factors to previous myocardial infarction. METHODS AND RESULTS: The fasting levels of C3, insulin, and the main risk factors were evaluated in 1090 unselected men aged 55-64 years, including 129 cases of previous ischaemic events (51 myocardial infarctions). In multivariate analysis C3 was associated with insulin (r=0.27, P<0.0001), cholesterol (r=0.18, P<0.0001), body mass index (r=0.13, P<0.0001), glucose (r=0.12, P=0.0001), systolic blood pressure (r=0.10, P<0.001), triglycerides (r=0.09, P<0.01) and HDL-cholesterol (r=-0.06, P<0.05). These variables explained 31% of the total C3 variance. Alcohol consumption and physical activity correlated inversely with C3, while no correlation was found with smoking and family history of myocardial infarction. C3 was associated with previous myocardial infarction and stroke, but not with angina pectoris and peripheral arterial disease. In logistic regression the variables associated with previous myocardial infarction were C3 (P=0.011), family history of myocardial infarction (P=0.018), ex-smoker status (P=0.020), age (P=0.025), glucose (P=0.028) and HDL-cholesterol (P=0.051, inverse relationship). CONCLUSIONS: The association of C3 with myocardial infarction persists retrospectively, and is more significant than any other association of traditional risk factors with previous myocardial infarction. Of the many variables associated with C3, fasting insulin is its main covariate, which suggests that C3 is a marker of a pro-atherogenic metabolic imbalance partly coinciding with insulin resistance.

Repolarization changes in a double-blind crossover study of dofetilide versus sotalol in the treatment of ventricular tachycardia.

UNLABELLED: The aim of this study was to determine whether a therapeutic response to Class III antiarrhythmic drugs is related to predictable changes in repolarization on the electrocardiogram (ECG). A group of 57 patients with ischemic heart disease and inducible ventricular tachycardia (VT) at electrophysiological study (EPS) were selected from a population enrolled in a randomized double-blind crossover study of dofetilide (500 micrograms bid) versus sotalol (160 mg bid). ECGs were analyzed blindly, and RR, QT (maximum value/12 leads), QTc (Bazett's formula), QT dispersion (QTmax-QTmin over 12 leads) and QTc dispersion, were calculated at baseline and on the third day of treatment (4 hours after dosing), when patients underwent EPS to test the effects of study drugs on VT inducibility. RESULTS: At EPS 21 patients were responders to dofetilide and 22 to sotalol. On day 3, a significant increase in QT and QTc and decrease in QT and QTc dispersion, compared to baseline, was measured in responders and nonresponders, with both dofetilide and sotalol. No significant difference in QTc or QT dispersion between responders and nonresponders was observed in either treatment group. In conclusion, treatment with dofetilide and sotalol was associated with an increase in QT and QTc, and a decrease in QT and QTc dispersion. In contrast with previous reports, a differential effect on QT or QTc dispersion was not observed in drug responders versus nonresponders.